Psychiatric symptoms in neurological practice

M Madhusudanan Department of Neurology, Medical College Hospital, Kottayam, Kerala, India Introduction

In clinical practice, many patients who present with or are brought with so-called primary psychiatric symptoms like delusions, hallucinations, behavioral and personality changes etc. pose problems to the treating physician as to whether these symptoms are due to organic diseases affecting the brain or primary psychiatric illnesses.

This article is intended to offer a brief outline as to how to diagnose organic causes when the patients primarily present with psychiatric symptomatology.

Delusions

Delusions are false beliefs despite evidence to the contrary.

Cummings[1] proposed four types of delusions in his study of 20 patients "with organic delusions." They are: a) simple persecutory delusions, b) complex persecutory delusions, c) grandiose delusions and d) delusions associated with specific neurological defects-anosagnosia and reduplicative paramnesia.

Simple persecutory delusions consist of elementary, loosely structured beliefs that are usually transient, such as believing that possessions or money are being stolen or that one's spouse is unfaithful. Cummings[1] found that simple delusions were often encountered in patients with Alzheimer's disease and vascular dementia.

Complex delusions have a more rigid and stable structure and they are associated with substantial, though distorted, observation. Schneider's first-rank symptoms of schizophrenia and monosymptomatic delusions such as the Capgras syndrome are included in this category. Examples of complex delusions include patients' beliefs that the radio or TV is sending out messages to them, that the street lights are being focused on them, that others around them are talking about them or that people are plotting to steal their homes. Patients with Capgras syndrome have the false belief that significant people have been replaced by identical appearing impostors. Two other syndromes that share features with the Capgras syndrome are the Fregoli syndrome, where patients identify their persecutor in several different persons (the persecutor being accused of changing faces like an actor) and the intermetamorphosis syndrome, where patients believe that people have taken on the physical appearance of others. Cummings[1] found that complex delusions occur in patients with hepatic encephalopathy, Parkinson's disease, posttraumatic encephalopathy and idiopathic calcification of the basal ganglia. Grandiose delusions were seen only in one patient with Huntington's disease.

Delusions associated with specific neurological conditions include reduplicative paramnesia-a state in which patients believe that they are simultaneously in two geographical locations. It is usually seen during recovery from acute cerebral lesions, as in posttraumatic encephalopathy or cerebrovascular disease. Reduplicative paramnesia has been associated with right parietal or combined right parietal and bilateral frontal dysfunction.[1] Other delusions with neurological defects include denial of blindness, as in Anton syndrome secondary to bilateral posterior cerebral artery occlusion and denial of hemiparesis (neglect syndrome), seen with right hemispheric infarction.

Cummings[1] observed that the complexity of delusions is related to the severity of intellectual impairment. He commented that the intellect is in the service of delusions. Patients who are moderately to severely cognitively impaired display simple delusions secondary to their poor judgment and reasoning capacity. However, patients who are much less cognitively impaired have greater ability to think and reason and thus have complex, elaborate delusions.

A wide range of neurological, toxic and metabolic disorders can lead to secondary delusions. Clinical features suggesting an organic aetiology include atypical age of onset, specially after age 45; absence of a family history of psychiatric illness; absence of any past psychiatric disturbances or premorbid behaviors characteristic of functional psychiatric disorders; presence of family history of neurologic disorders such as Huntington's disease; presence of focal neurological signs; presence of mental status deficits suggestive of focal or degenerative brain disorders; presence of unusual psychiatric syndromes or atypical mixed states (such as prominent mood changes with mood-incongruent delusions); history of a medical disorder or neurologic condition, even if remote; presence of unusual temporal features such as abrupt onset, quick resolution or rapid fluctuation; and treatment resistance or unusual treatment response.[2]

Delusions are not uniformly linked to specific anatomic structures in the same way that hemiparesis follows pyramidal lesion. It is more often seen with bilateral lesions than with unilateral lesions and in diseases affecting the temporal lobe cortex and basal ganglia especially caudate nucleus. When delusions occur with focal lesions, injury is usually in the right or left temporoparietal region: with left sided lesions delusions occur in conjunction with Wernicke's aphasia: with right sided lesions prominent visual hallucination commonly accompanies delusions.

Common diseases associated with delusions are given in [Table - 1].

In a study by Rubin[3] of 110 patients with Alzheimer's disease, 31% had paranoid delusions. The most common were delusions of theft in 28%. Delusion of suspicion was seen in 9%, more complex and systematized delusions were seen in 3.6% and 1 patient developed an erotomanic-like delusional symptom. Rubin concluded from his study that most delusions in Alzheimer's disease are uncomplicated; however, systematized complex delusions can occur.

Delusions are rare in Parkinson's disease and brain tumour. If it occurs in Parkinson's disease, it is usually a manifestation of dopamine or anticholinergic toxicity.

Most of the secondary delusions are manifested by paranoid delusions and ideas of reference and/or persecution. Schneiderian first rank symptoms have been reported in a number of neurological illnesses including epilepsy, Huntington's disease and idiopathic basal ganglia calcification.[4] In some cases, delusions have a specific theme or are confined to a single topic. The principal content specific delusions are listed in [Table - 2].

Neurophysiology of Delusions

Delusions may reflect dysfunction of the limbic system. Cummings[5] in his neurobiological model for delusions in neurological diseases reported that the two regions in the brain associated with delusions are the caudate nucleus and the temporal lobes, both portions of the limbic system. They are connected and innervated by the dopaminergic projections from brainstem nuclei. The cortical structures of the limbic system include the subcallosal gyri, cingulate gyri, parahippocampal gyri, hippocampus, posterior orbitofrontal cortex and anterior insular region. The nuclear structures of the limbic system include the amygdaloid complexes, septal nuclei,hypothalamus, epithalamus and anterior thalamic nuclei.[5]

The limbic system augments arousal and mediates environmental surveillance. Cummings[5]reported that dysfunction of the limbic system interferes with assessment of environmental threat, produces incorrect assessment of danger and causes inappropriate fear and threatened behavior. This is often manifested as paranoia. The individual may suspect the intentions of others and perceive menace and threat where none exist, resulting in persecutory ideation and inappropriate fear. Thus, there is an abnormal linkage between emotional content, current input and past memories.

At a neurobiochemical level, the dopaminergic/cholinergic balance may be crucial in the genesis of delusions. One study[6] has shown that psychosis is rare in untreated Parkinson's or progressive supranuclear palsy, both of which are characterized by marked dopamine deficiency. On the other hand, patients treated with dopaminergic agents and dopamine-treated Parkinson's patients have increased rates of psychosis.

In Alzheimer's disease, dopaminergic function is relatively preserved and there is deficiency of choline acetyl transferase with resultant deficiency of acetylcholine.[7] The severe deficiency of cholinergic function creates a marked imbalance between the two transmitters, causing a relative hyperdopaminergic state that may lead to the genesis of delusions. Cholinergic deficiency is most severe in the limbic regions, including the postcingulate gyrus, fusiform gyrus and anterior and inferior temporal regions.[7]

Autopsy studies of 27 cases of Alzheimer's disease with "psychosis" have shown that there is significant increase in density of senile plaques and neurofibrillary tangles in the presubiculum (allocortex), middle frontal cortex (neocortex), entorhinocortex and superior temporal cortex compared with patients who did not have psychosis.[8] The increased density of senile plaques and neurofibrillary tangles in the cerebral cortex of patients with psychosis may explain the association with more rapid cognitive decline.

Starkstein et al[9] compared SPECT scans of 16 Alzheimer's disease patients with delusions and 29 without delusions. Alzheimer's disease patients with delusions had significantly lower cerebral blood flow in both left and right temporal lobes as compared with the patients with no delusions. Deficits were similar in both the superior and the inferior temporal regions in patients with delusions. The study supported the suggestion by Cummings that damage to the temporal lobe may underlie the presence of delusions in Alzheimer's disease.

How to differentiate delusions of organic CNS disease from primary psychiatric diseases?

1. Even though any type of delusional content can be seen in organic delusions, most delusions in neurological illness tend to be persecutory beliefs.

2. Delusions are more common in diseases affecting both cerebral hemispheres such as degenerative diseases and vascular dementia. Patients with dementing illnesses have mainly simple delusions, where as patients with single stroke or other limited lesions exhibit complex, well structured firmly held beliefs i.e., The more intact the patient's cognition, the more complex the delusions tend to be.

3. When the delusions follow unilateral lesion the laterality of the damage may influence the delusional content. Schneiderian first rank symptoms are more common with left sided lesions and delusions of substitution and misidentification syndrome such as Capgras syndrome are more common with right hemispherical lesions.

4. Cognitive abnormalities indicative of frontal and temporal lobe abnormalities are common in patients with organic delusions.

5. Visual hallucinations are commonly associated with delusions in neurological illness than primary psychiatric disease where as complex auditory hallucinations usually accompany delusions in primary psychiatric illness.

6. It is common for the onset of delusions to be delayed for considerable period of time after the occurrence of brain insult. In temporal lobe epilepsy, for e.g., several years may elapse between the occurrence of brain injury with the onset of seizure and the first appearance of delusions.

Hallucinations

Hallucinations are sensory perceptions occurring without the appropriate stimulation of the corresponding sensory organ.

Visual hallucinations

When simple visual hallucinations occur, they are almost always organic. The problem arises when the patient experiences complex visual hallucinations.

Visual hallucinations are common in neurological illness. The differential diagnosis of visual hallucinations is presented in [Table - 3]. Ocular diseases that produce total or partial blindness-enucleation, cataracts, macular degeneration, retinal diseases or vitreous traction-are common causes of hallucinations. Vitreous traction produces unformed flashes of light; the other processes may produce formed or unformed hallucinations. Inflammation of the optic nerves from ischemic optic neuritis or optic nerve demyelination can cause phosphenes or unformed flashes of light.

Complex visual hallucinations, such as landscapes or animals, are related to temporal lobe dysfunction. Besides complex visual hallucinations.[10],[11] Some authors have mentioned simple, occipital-like visual experiences in temporal lobe seizures.[12],[13] Among structural lesions tumors have the greatest tendency to induce hallucinations.

Migraine is the most common single cause of visual hallucinations and illusions. Elementary visual disturbances can include phosphenes (simple flashes), scotomata, specks, colored or black and white geometrical forms or shimmering images. These may occur singly or in multiple forms. They often present in a hemi-field distribution but may occur directly in front or in an arc in front of the patient. The patient with migraine aura can also experience more complex visual phenomena. The most common of these is the teichopsia or fortification spectra. Patients with migraine may also experience metamorphopsia, micropsia and macropsia ( Alice in Wonderland syndrome ^{More Details}). In some patients complex visual images occur with multiple figures including animals, people and elaborate scenes.

Posterior cerebral infarctions can also lead to hallucinations. The lesions involve the occipital lobes and often the thalamus as well. The hallucinations are most of-ten restricted to the side with the abnormal visual field. The pathology is usually ischemic infarction and may be delayed days to weeks after the infarct before the hallucinations begin. Most often they last several days to weeks, but may persist longer.

Narcoleptic hallucinations are termed hypnogogic (entering sleep) and hypnopompic (awakening). Hallucinations in this disorder last several minutes and are present in some 30% of narcoleptics. The hallucinations can be visual, auditory or tactile, but typically not olfactory. They may consist of colorful images, which may involve people, animals and panoramic scenes. Unlike dreams, there is no clear thematic content present in the hallucinations.

Patients with epilepsy may also experience perceptual abnormalities. The hallucinations are usually brief, stereotyped and fragmentary and may be in black and white or color. Rarely, hallucinations may be more complex and resemble those seen in narcolepsy. Occipital lobe seizures in adults most commonly present with simple visual phenomena. Patients may experience negative symptoms such as scotomata, amaurosis or hemianopsia or more commonly unformed positive symptoms such as phosphenes. These may be described as sparklers or pinwheels.

If the focus is in the temporo-parieto-occipital region, patients may describe illusions in which objects appear to be distorted. This can involve changes in size including micropsia or macropsia, change in shape (metamorphopsia), colorful scenes of varying complexity and the illusion that the patient is outside his or her own body (autoscopy).

Several features help to separate occipital lobe seizures from migraine headaches even though at times this can be quite difficult. In occipital lobe epilepsy, the visual hallucinations are stereotyped for each patient and last 5-30 seconds rarely up to 1 minute. There are no consistent precipitating factors present. Occipital lobe seizures tend to occur daily and consist mainly of multiple, bright-colored circular images that are most often seen in the temporal field and move contralaterally but may begin centrally. Occipital lobe seizures may be followed by a headache that is indistinguishable from a migraine. By contrast, migraine patients more often have a family history of headaches, the hallucination (aura) occurs several times a week to month and not daily and the headaches last hours to days.

Yet another situation of complex visual hallucination that is seen is with Charles-Bonnet syndrome. This is due to impaired vision typically with visual acuity of 20/50 or less (release hallucination). These recurrent vivid hallucinations occur in the presence of normal cognition and insight and are usually associated with severe visual deprivation.[14] The hallucinations usually occur in the evening and are often made up of small, brightly colored people or objects with a cartoon like appearance. They may range in complexity from simple phosphenes to well-formed visions, such as people, vehicles or furniture. The patient is usually aware of the unreality of these hallucinations and may note that the hallucinations change size or character when the subject reaches out to touch them.

These hallucinations are less stereotyped from episode to episode, longer in duration or continuous (minutes or hours at a time), likely to occur in the blind portion of the visual field and perceived as unreal by the patient[15] and may be modified by moving or closing the eyes. Release hallucinations are thought to represent the liberation of endogenous cerebral visual activity from "control" by higher visual inhibitory centers and may result from lesions anywhere in the visual pathways (retina to occipital cortex), regardless of the complexity of the hallucination.[16]

Lesions of midbrain and thalamus[17] may cause complex visual hallucinations that have an oneroid (dreamlike) quality (peduncular hallucinosis). Peduncular hallucinations are often hypnagogic, are usually known to be unreal, may be of normal or Lilliputian proportions and may be pleasant to the patient. They usually occur in the evening and associated with a benign affect. A sleep disturbance is usually present. The condition rarely last for more than a day. Peduncular hallucinosis has been postulated to be a release phenomenon related to damage to the ascending reticular activating system (ARAS).[17]

Visual hallucinations are common in delirium associated with toxic or metabolic encephalopathies, in alcohol or sedative-hypnotic withdrawal and with ingestion of hallucinogens such as lysergic acid diethylamide (LSD), psylocibin and mescaline and dissociative agents such as phencyclidine (PCP). Visual hallucinations are also reported in Lewy Body Disease and are related to Lewy Bodies in the temporal lobe.[18] Visual hallucinations occur in up to 30 percent of patients with Parkinson's disease treated with dopaminergic agents (e.g., levodopa, bromocriptine, pergolide). Dementia is a common predisposing factor in Parkinson's disease patients with hallucinations.

Visual hallucinations occur in idiopathic psychoses including schizophrenia, depression and mania. They are rarely the dominant type of hallucination in these circumstances. Normal individuals may experience visual hallucinations on falling asleep or in the course of sensory or sleep deprivation. The imaginary companions of childhood often have a visual aspect.

Focal seizures arising in the neocortex of the temporal lobe give rise to visual illusions ("deja vu," already seen; "jamais vu," never seen before) or to experiential illusions ("deja vecu," already lived; "jamais vecu," never experienced before). The patient feels a strong sense of familiarity with scenes or experiential situations that in reality he or she has never seen or experienced before or, on the contrary, a sense of strangeness about visual stimuli such as the face of close relative or experiential situations that should be familiar.

Hallucinations in other sensory modalities are less common than visual hallucinations in neurological illnesses.

Auditory hallucinations

Standard medical teachings suggest that auditory hallucinations most often indicate primary psychiatric problem, but one should remember that auditory hallucination can also occur due to organic CNS disease.

Tinnitus is almost always organic. Palinacousis, the continued recurrence (echo) of a prior auditory perception resembles palinopsia, but is less common. Some cases are related to temporal lobe epilepsy.[19] Auditory hallucinations can occur as auras of temporal lobe epilepsy. At times, focal pathology in the temporal lobe may be associated with sounds and voices that are independent of reality, but occur without overt seizure activity and can be confused with psychiatric illness.[20]Auditory hallucinations have also been reported in patients with pontine lesions.[21],[22]

Withdrawal states especially from alcohol can cause auditory hallucination that feature voices that are self deprecating and/or threatening.[23] They tend to affect older individuals with a long record of heavy alcohol consumption.

Auditory hallucination due to primary psychiatric illness is often difficult for the patient to localize in space (often sensed as occurring inside the head). The voice most often comments on the patient's behavior and /or echos the patient's thoughts.

Auditory hallucinations occur in conjunction with persecutory delusions in the delusional disorders. They may also occur with deafness, brainstem lesions and epilepsy.

Gustatory hallucinations

Gustatory hallucinations are usually associated with temporal lobe lesions and uncinate gyrus fits[24] and are usually unpleasant.[25]

Olfactory hallucinations

Olfactory hallucinations are reported in temporal lobe epilepsy and are distinguished from those occurring in psychiatric disorders by absence of associated delusions and recognition of the symptom as a part of the illness.[26] Olfactory hallucinations are also found in patients with migraine.[27]

Haptic/pain hallucination

Somasthetic (Haptic) hallucinations include both unusual bodily experiences and pain. Following limb amputation, a hallucination of phantom limb pain is almost universal and pain in non-existing limb is present in as many as 85% of post amputation patients.[28],[29] Hallucinatory duplication of the limb or other body segment or a sensation of distorted body shape may occur with migraine, as an epileptic aura, with toxic encephalopathy or following the use of hallucinogenic drugs.

Formication hallucination, the feeling that bugs are crawling on the skin, occur in variety of neurological and psychiatric conditions.[30] They are common in alcohol and drug withdrawal states and occur in a number of toxic and metabolic conditions. If the sensation is unilateral, formication hallucination may indicate thalamic or parietal lesion.[31],[32]

Tactile hallucinations are reported in delirium, withdrawal states (particularly opiate withdrawal) and in association with delusions of infestation. Gustatory and olfactory hallucinations occur in psychoses and epilepsy.

Depression

Depressive symptoms are common in neurological diseases. In some cases, depression is reactive to the neurological disability or to the increasing dependence on others. In many, however, the depression is more severe than anticipated for the functional disability. In these conditions the depression is a behavioral manifestation of the brain dysfunction.

Neuroanatomy of depression

To what extent lesion in specific cerebral areas can produce de novo affective illness is still controversial. Studies correlating lesion sites (as evidenced by CT scan, MRI and PET) with symptoms of depression have not demonstrated any specific depression inducing location. Most studies have shown that the lesions in the anterior parts of the both cerebral hemispheres are more likely to produce depression than more posterior lesions. Lesions isolated to basal ganglia have been associated with depression where as lesions in the thalamus have not.[33]

Studies in stroke patients have shown that left sided lesions are more often associated with depression than right hemispherical lesions.[34] It has also been found to be more common in non-fluent aphasic patients compared to fluent aphasics.[35]

Depressed mood is more often associated lesions of frontostriatal and paralimbic pathways. Lesion-deficit and functional imaging studies of depressed neurological patients have consistently identified involvement of frontal and temporal cortices and striatum.[36] These common abnormalities have been interpreted as evidence of disease-specific disruption of known neurochemical pathways involving frontal-striatal-thalamic and basotemporal limbic circuits.[37]

Depression has, in addition to changes in the mood, changes in cognition and attention evidenced by apathy, psychomotor slowing, impaired attention and changes in visceral and vegetative function in the form of alteration in sleep, appetite, libido and endocrine function.

Failure of a coordinated interaction within a network of limbic-cortical pathways has been postulated as a model for depression. In this model there are two compartments:

a. A dorsal compartment: this includes the neocortex (specifically orbitofrontal cortex and dorsolateral prefrontal cortex) and the anterior cingulate cortex. This compartment is postulated to mediate the attentional and cognitive features of depression such as apathy, psychomotor slowing and impaired attention. Intrinsically generated willful behavior is associated with activation of dorsolateral prefrontal cortex as well as anterior cingulate gyrus and SMA. Psychomotor retardation seen in depression reflects a disturbance in this "volitional action system".

b. A ventral system which include the medial orbitofrontal cortex, limbic and paralimbic region and the ventral anterior cingulate cortex. Medial orbitofrontal and ventral anterior cingulate gyrus has reciprocal connection with phylogenitically older basolateral amygdala. This amygdalar region subserves the synthesis of internal mood and visceral function. Thus this ventral compartment is thought to mediate the vegetative and visceral aspects of depression like changes in sleep, appetite, libido and endocrine function.

Pitfalls in the diagnosis of depression

In some instances depression may be over diagnosed and in some situations, one may overlook the diagnosis of depression.

Many neurological diseases by themselves can produce depressive symptoms without any mood changes. For example, diminished pleasure and interest, weight loss, insomnia, agitation and psychomotor slowing, fatigue and impaired concentration can occur due to the neurological illness per se without patient himself not feeling depressed and he may be mistakenly diagnosed to be a case of depression. Other neurological illnesses, such as the parkinsonian disorders, produce psychomotor slowing, stooped posture, fatigue and impaired concentration resembling depression; depression in these disorders may be over diagnosed.

Some right hemispherical lesions produce abnormalities in affective components of language (aprosodias). These patients have problems with comprehension of emotionality, wit and humor and with understanding the proper facial expression that accompany speech (sensory aprosodias). Some others have problems with emotional gesturing. Patients experience various degrees of difficulty expressing the appropriate emotions including happiness and anger (body language) responding correctly to those cues expressed by others (motor aprosodias). Thus a patient who is not depressed might be mistakenly described as depressed, owing to the lack of synchrony between language output (and thoughts) and emotional prosodic expression.

Experiential manifestations of depression including feelings of sadness, worthlessness, hopelessness and recurrent thoughts of death or suicide are the most dependable indicators of a depressive syndrome and should be carefully sought.[2] Dementia patients, however, may be unable to describe these subjective symptoms and depression must be inferred from the associated symptoms.

Similarly a depressed patient may be mistakenly diagnosed as demented (depressive pseudodementia). [Table - 4] gives the clinical features differentiating depressive pseudo-dementia from dementia.

Neurological diseases associated with depression

Neurological diseases in which depression has been identified as a prominent abnormality include

1. Dementing diseases.

a. Alzheimer's disease.

b. Frontotemporal dementia.

2. Extrapyramidal disorders.

a. Parkinson's disease.

b. Huntington's disease.

c. Wilson's disease.

d. Idiopathic basal ganglia calcification.

3. Stroke and vascular dementia.

4. CNS Infections.

a. Viral encephalitis.

5. Multiple sclerosis.

6. Epilepsy.

7. Endocrine disorders.

a. Hyperthyroidism.

b. Hypothyroidism.

8. Systemic illnesses.

a. SLE.

9. Medications.

Depression is more often seen in lesions of frontal subcortical system structures.

Depressive symptoms may differ subtly in different neurological disorders. Suicide is common in Huntington's disease and epilepsy, but rare in Parkinson's disease; the depression of Parkinson's disease is characterized by more anxiety and less guilt than primary depressive disorders. Psychomotor retardation is more extreme in post-stroke depression than in other depression syndromes. Depression in neurological diseases usually responds to treatment with psychopharmacological agents or electroconvulsive therapy. Depressive disorders with specific illness are associated with a cluster of psychological (behavioral) and physiologic symptoms (biologic and vegetative).

Mania

Mania is much less common than depression in the course of neurological illness.

Neuroanatomy of mania

Structural lesions producing mania usually involve the basotemporal region, head of caudate nucleus, parathalamic structures or the inferior medial frontal lobe.[38],[39]

When lateralized, the lesions have had a marked right-sided predominance. A family history of psychiatric illness is more common in patients with secondary mania than in normal controls and genetic vulnerability may facilitate the appearance of mania in the setting of brain dysfunction.

Several studies have shown that amygdala plays an important role in the production of instinctive reaction and in associating emotional response with the stimulus.[40] The amygdala receives its main afferents from the basal diencephalon (which in turn receives psychosensory and psychomotor information from the reticular formation) and basotemporal cortex. The basotemporal cortex receives afferents from association areas and the orbitofrontal cortex.[41] Anterior orbitofrontal cortex exerts a tonic inhibitory control over amygdala by means of its connection through uncinate fasciculus.[42]

Mania is supposedly due to dysfunction of the orbitofrontal-amygdela-hypothalamic circuit.[43]Disinhibition due to orbitofrontal lesions will affect motor activity in general, the thought processes and a variety of instinctual impulses. Orbitofrontal hyperactivity gives the appearance that the patient has excessive drive that he or she can not concentrate on anything and is driven by an incessant necessity to act, albeit in a haphazard and purposeless fashion. This apparently boundless energy and impulsivity may interfere with sleep and orderly thought process. Because of the disinhibition of the basic drives, the patient may display hyperphagia and hypersexuality in utter disregard of common social mores and conventions.[44] Because of the euphoria, uncontrolled thinking and behavior and the insomnia, patient with orbitofrontal syndrome may be mistaken for mania. Only a thorough history and meticulous neurological examination can exclude a primary psychiatric illness.

Even though orbitofrontal patients show impairment of behavior necessary for activities of daily living, they have normal performance on neuropsychological tests of frontal lobe dysfunction. Mendez et al[45] showed that patients with ventral caudate lesions were disinhibited, euphoric, impulsive and inappropriate, recapitulating the corresponding orbitofrontal (OF) lobe syndrome. It is likely that the early appearance of similar personality alterations in Huntington's disease reflects the involvement of medial caudate regions receiving projections from the OF and anterior cingulate circuits that mediate limbic system function.[46] Similarly, mania may result not only from injury to medial OF cortex and caudate nuclei (e.g., Huntington's disease) but also from lesions to the thalamus. More commonly orbitofrontal syndrome is characterized by labile mood with a general tendency for euphoria. The latter may be accompanied by a form of silly, compulsive childish humor that has been called moria (Witzelschut).

Diseases associated with mania

Maniform symptoms have been observed in:

1. Huntington's disease.

2. Wilson's disease.

3. Idiopathic basal ganglia calcification.

4. Stroke.

5. Trauma.

6. Multiple sclerosis,

7. General paresis.

8. Viral encephalitis and postencephalitic syndromes.

9. Frontal degenerative disorders.

10. Following thalamotomy.

11. Drugs.

a. Steroids.

b. Benzodiazepines.

c. Dopaminergic agents.

d. Thyroid preparations.

e. Sympathomimetics.

f. Stimulants.

g. Antidepressant agents may precipitate manic episodes in depressed patients.

Neurology of Aggression

Aggressiveness is an integral part of social behavior. It is present even in lower forms of animals. Aggression can be divided in to various types according to the triggers: predatory offensive aggression, inter-male (competitive) aggression, fear induced aggression, maternal protective aggression and sex related aggression.

In humans, the control of aggression is present in the brain stem and hypothalamus as in lower animals. A second critical level of control in the mammalian brain is provided by the limbic structures each of which project to the hypothalamus. A third level, greatly expanded in higher primates is the frontal neocortex modulating both limbic and hypothalamic out put. These levels are functionally distinctive.[47]

Hypothalamic regulation

Ventromedial lesions of hypothalamus in humans produce aggressive behavior.[48],[49],[50] The patients so afflicted may attack the attenders and doctors. Often these hypothalamic aggression is not associated any mood changes like anger. Patients deny any anger or vindictive internal feelings towards the individuals they attack. Often the attacks are provoked by hunger and by seasonal variation.

Amygdala and temporolimbic regulation

In contrast to the hypothalamus, the amygdaloid complex is reciprocally connected with multiple cortical sensory systems capable of conveying highly processed information regarding external world. Rich connections are established with all polymodal sensory areas, allowing convergence of information from visual, auditory, tactile and gustatory cortices.[51],[52]

Important outputs from amygdala are to the hypothalamus through stria terminalis and the ventral amygdalofugal pathway and to brain stem centres controlling the heart rate and respiration and to extrapyramidal motor system especially ventral striatum (also through the stria terminalis and the ventral amygdalofugal pathway).

The amygdala appears to provide a critical link between the sensory input processed in the cerebral cortex to produce a model of external reality and the hypothalamic and somatomotor centres evoking pain, fear and other drive related emotions.[53] The amygdala is important in finding the affective significance of the stimuli as exemplified by the drive-object dysregulation seen in Kluver-Bucy syndrome.[54] Amygdala lesions results in taming and placidity.[55] Objects that previously evoked signs of fear or provoked attack seem to lose their past associations. The fundamental effect of amygdalectomy on aggression is not a change in the aggressive threshold, but a modification of previously acquired pattern of linking stimuli with aggressive responses.[56]

Patients with lesion of amygdala have difficulty in identifying particular objects as being appropriate or inappropriate for satisfying the hypothalamic drives. Hence they fail to distinguish food from inedible objects and eat whatever they see and have difficulty in distinguishing appropriate from inappropriate sexual partners.[54],[57] Fundamental drives such as feeding and reproduction are released on to inappropriate targets.

In human, stimulation of cortico-medial amygdaloid nucleus evokes a display of anger where as stimulation of basolateral nucleus does not. Destruction of amygdaloid nuclear complex bilaterally will abolish aggression. Lesions of dorsomedial nucleus of thalamus which receive projections from the amygdaloid nuclei render humans more placid and docile. Similarly bilateral ablation of neocortical area 24 (rostral cingulate gyrus) has produced the same effect; i.e., tameness and reduced aggression.

Patients with Kluver-Bucy syndrome (bilateral temporo limbic damage) engage in indiscriminate oral and tactile exploration of their environment (hyperorality and hypermetamorphosis) and change their sexual preferences. Such individuals exhibit a flattened affect and report diminished subjective emotional response to stimuli.[58] Aggressive behavior becomes uncommon and apathy and placidity occurs.

The emotional disconnection can be modality specific in strategically placed lesions;[59],[60] e.g., visual hypoemotionality (i.e., an isolated inability to react affectively to visual stimuli) due to bilateral inferior temporooccipital lesions. Patients with such lesions may complain of total loss of emotional reactions to seeing attractive women or erotic visual stimuli and find natural scenery as dull. On the contrary, he could be sexually aroused by verbal-auditory stimuli and derive pleasure by touching and being touched. The modality specific limbic disconnection may extend to fear and aggressive responses.

Sometimes the converse of what is seen in Kluver-Bucy syndrome can be seen. This is usually seen in temporal lobe epilepsy in which abnormal neuronal excitability develops within temporolimbic cell population. Amygdaloid complex is particularly sensitive to kindling in which repeated stimulation of neurons leads to progressive lowering of the threshold for discharge. As a result, the patients have enhanced aggressive and other emotional responses to both drive related and neutral stimuli.[61],[62] They exhibit deepened and generalized affective association. This phenomenon, Geschwind syndrome, characterized by deepening emotions, sensitivity to moral issues, often with religious and philosophical preoccupation and hypergraphia - a tendancy to write at great length-can be seen in interictal period between seizures.[63],[64] As a consequence of the strongly felt emotions, these patients may become very sensitive to slight issues or violation of principles and experience intense anger. Strong moral and philosophical beliefs often preclude violent acts. However, even though the patients do act aggressively, their behavior typically is performed in clear consciousness and often followed by sincere regret.

Neocortical regulation of aggression

Neocortical regulation of aggression is mediated mainly by orbitofrontal cortex.

Projections from the hypothalamus through the dorsomedial nucleus of thalamus and from the rostral temporal lobe through the uncinate fasciculus potentially inform the frontal lobe of both internal (hypothalamus) and external (neocortical association to temporal lobe) stimuli of affective significance.[47]

The prefrontal cortex integrates the current account of the external world, the state of internal milieu and the drive-relevant stimuli with knowledge of the learned social rules and previous experiences relating to reward or punishment. Prefrontal lobe anticipates to the effects of one's action upon other individuals and the likely consequences of such action based on past experience; and the prefrontal cortex construct a behavioral plan that is consistent with past experience and the rules of socialization in order to optimize the satisfaction of biological drives. These features constitute the "judgment".

Damage to the orbitofrontal cortex results in superficial, reflexive emotional responses to stimuli in the immediate environment.[65] Patients are impulsive without foresight or consideration of the remote consequences of their action. Orbitofrontal lesion thus leads to irritability and aggressive behavior on trivial provocation with little consideration to social prohibitions. The targets of aggression are categorically appropriate, but patients are unable apply abstract rules that would override the immediate environmental provocation.

Rage reaction has been observed in the following medical settings:

1. As an ictal or more often post ictal phenomena.

2. As an episodic reaction without recognizable seizure or any other neurological abnormality (episodic dyscontrol). Depth electrode recording in these situations have shown spike potentials from the amygdaloid nucleus.

3. In the course of a recognizable acute neurological illness: e.g., hemorrhagic leucoencephalitis, lobar hemorrhage, infarction, herpes simplex encephalitis affecting the orbitofrontal portion of the frontal lobe and inferomedial portion of the temporal lobe.

4. With clouding of consciousness that accompany the delirium.

Personality Alterations

Personality refers to stable patterns of behavior that include the way one relates to, perceives and thinks about the environment and oneself. This is the least explored area of neuropsychiatry. Personality changes have been difficult to quantify for study and personality alterations may be difficult to distinguish from the delusional and mood disorders that also occur in neurological illness. [Table - 5] summarizes the personality alterations observed in specific neurological diseases and conditions.

Focal lesions also may be associated with personality alterations. The marked personality alterations occur following orbitofrontal and medial frontal lesions.

Orbitiofrontal syndrome

The orbitofrontal cortex is the neocortical representation of the limbic system[42] and is involved in the determination of the appropriate time, place and strategy for environmentally elicited behavioral responses. Lesions in this area appear to disconnect frontal monitoring systems from limbic input, resulting in behavioral disinhibition and prominent emotional lability.

Disinhibition and impulsivity of thought, affection and action

1. Patients lack judgement and social tact and may exhibit inappropriate jocularity (witzelsucht). Decreased impulse inhibition may be associated with improper sexual remarks or gestures and other antisocial acts, although overt sexual aggression is rare.[65] The lesions of orbitofrontal lesions may remove the moral-ethical restraint and lead to indiscriminate sexual behavior. Patients may appear irritable and trivial stimuli may result in outbursts of anger that pass quickly without signs of remorse.[66] Inattention, distractibility and increased motor activity may be seen and hypomania or mania is not uncommon. With OF lesion, the behavioral changes are difficult to measure. However, the family members will tell that the person is no longer the same. For e.g., the patients may drive past the stop signals, fail to show concern, become slovenly and unkempt, joke about some one's physical deformity in front of them, become violent after minor provocation and quickly return to their previous calm state or urinate in the public. The patients do fairly well on standardized tests, but fail at life. Although frequently incontinent, they are unconcerned and almost never initiated an attempt to remedy the status."

2. Failure to appreciate consequences of one's action. These patients are unable to anticipate the consequences of any action and act impulsively and reflexively.

3. A flat affect, blunted emotional response and decrease in drive.

Patient is usually quiet, remote and withdrawn and do not initiate conversation.

4. A lack of self-awareness regarding alterations in behavior, emotions and thought processes. Awareness may be considered one of the highest cognitive attributes of the frontal lobes. Patient is unable to monitor her or his own behavior and denies any disability and insists that he can return to work at any time.

5. Imitation and utilization behavior.

Large bilateral OF lobe lesions in man may, in addition, result in enslavement to environmental cues, with automatic imitation of the gestures of others or enforced utilization of environmental objects.[67] Patients with prefrontal lesions display a remarkable tendency to imitate the examiner's gestures and behaviors even when no instruction has been given to do so and even when this imitation entails considerable personal embarrassment. Also the mere sight of an object may elicit the compulsion to use it, although the patient has not been asked to do so and the context is inappropriate -as in a patient who sees a tongue depressor and proceeds to give the physician a checkup. These symptoms have been called the "environmental dependency syndrome". It has been postulated that the frontal lobes may promote distance from the environment (avoidance reaction) and the parietal lobes foster approach toward one's environment (approach behavior). Therefore, loss of frontal inhibition may result in overactivity of the parietal lobes. A given stimulus would automatically call up a predetermined response regardless of context.

6. Separation of action (response) from knowledge. (Lack of error correction).

While patients with frontal damage have little impairment of basic cognitive functions such as language and visuoperception, they may have difficulty using these skills. The patient tends to repeat the same mistakes in his daily life, even though the mistakes have been pointed out to him. His knowledge could not be used to control his actions.

These incapacities are not due to any difficulty in understanding the instructions, but it is related to an inability to evaluate errors, especially self-produced errors. Their problem is not one of error recognition or error evaluation, but one of error utilization. There is in fact dissociation between knowing and doing (a dissociation between thought and action). One has only to think about the consequences of even one error in the programme of operating machine or flying a plane.

Patients with Wernicke's aphasia are often suspicious, demanding, aggressive and irritable. Preliminary studies of adults with right hemisphere lesions suggest that they may exhibit alexithymia with reserved expression of emotions and a tendency to forego symbolic thought. Right hemisphere damage sustained in childhood may result in a schizoid type of behavioral pattern, perhaps because the inability to perceive or execute emotional cues limits the child's ability to engage in interpersonal relationships.

Limbic system lesions have profound effects on personality. Ventromedial hypothalamic lesions produce a syndrome of dementia, hyperphagia and rage. Bilateral medial temporal lobe lesions produce the Kluver-Bucy syndrome of placidity, hypersexuality and altered sexual behavior, visual agnosia, hypermetamorphosis (compulsive exploration of environmental stimuli) and hyperorality.

Alzheimer's disease has a profound impact on personality and the behavioral changes may predate the neuropsychological deficits. Early in the illness, patients become disengaged and indifferent, showing little concern about their own disease or insight into the feelings of family members. Late in the course, impulsiveness and aggression are often exhibited. Patients with other dementia syndromes exhibit contrasting personality alterations. Frontotemporal dementias such as Pick's disease usually produce disinhibition, impulsiveness and facetiousness characteristic of orbitofrontal dysfunction or apathy suggestive of medial frontal pathology. Huntington's disease combines marked irritability with impulsiveness sometimes leading to aggression, violence and suicide. Many subcortical dementias (e.g., Parkinson's disease, progressive supranuclear palsy, HIV encephalopathy) cause apathy and indifference.

A controversial area of research in neuropsychiatry concerns personality changes in epilepsy. Personality inventories reveal that the most common type of personality change in epilepsy patients is increased suspiciousness and paranoia. An uncommon syndrome (known as the temporal lobe epilepsy personality or Geschwind's syndrome) occurring in patients with partial complex seizures consists of hypergraphia, circumstantiality, interpersonal viscosity, hyperreligiosity and hyposexuality. This personality style is not unique to epilepsy but occurs with increased frequency in patients without epilepsy and can be the presenting manifestation of the limbic seizure disorder.

Anxiety

Anxiety is a state of apprehension, tension or uneasiness that occurs in anticipation of internal or external danger. The anxiety syndrome includes motor tension, autonomic hyperactivity, apprehensive expectation and heightened vigilance. Anxiety occurs in a variety of neurological and medical disorders and can be precipitated by drugs. Neurological diseases causing anxiety include brain tumors (particularly in the regions of the temporal lobe or third ventricle), trauma, stroke, migraine, encephalitis, multiple sclerosis, epilepsy, Alzheimer's disease, Parkinson's disease, Huntington's disease and Wilson's disease. The principal medical conditions associated with anxiety include hypoxia, hypoglycemia, hyperthyroidism and Cushing's disease. Medications associated with anxiety include levodopa, tricyclic antidepressants, bupropion, fluoxetine, isoniazid and thyroid hormones.[2] Post-stroke anxiety is more likely to occur with left anterior cortical lesions.[68] A relationship has been found between anxiety or panic and temporal lobe lesions, predominantly those affecting right-sided structures.[69]

A panic attack is a discrete episode of intense fear or discomfort which starts abruptly and reaches a maximum within a few minutes and lasts at least some minutes. The various associated symptoms include autonomic arousal symptoms in the form of palpitations or pounding heart or accelerated heart rate; sweating; trembling or shaking; dry mouth (not due to medication or dehydration); symptoms involving chest and abdomen in the form of difficulty in breathing; feeling of choking; chest pain or discomfort; nausea or abdominal distress (e.g., churning in stomach); symptoms involving mental state in the form of feeling dizzy, unsteady, faint or light-headed; feelings that objects are unreal (derealization) or that the self is distant or "not really here" (depersonalization); fear of losing control, "going crazy," or passing out; fear of dying and general symptoms in the form of hot flushes or cold chills; numbness or tingling sensations.

Panic disorder must be differentiated from a number of medical conditions that produce similar symptomatology. Panic attacks are associated with a variety of endocrinological disorders, including hypo- and hyperthyroid states, hyperparathyroidism and pheochromocytomas. Episodic hypoglycemia associated with insulinomas can also produce panic like states, as can primary neuropathological processes. These include seizure disorders, vestibular dysfunction, neoplasms or the effects of both prescribed and illicit substances on the central nervous system. Finally, disorders of the cardiac and pulmonary systems, including arrhythmias, chronic obstructive pulmonary disease and asthma can produce autonomic symptoms and accompanying crescendo anxiety that can be difficult to distinguish from panic disorder. Clues of an underlying medical cause for panic like symptoms include atypical features during panic attacks, such as ataxia, alterations in consciousness or bladder dyscontrol; onset of panic disorder relatively late in life or physical signs or symptoms indicating a medical disorder.

Panic disorder also must be differentiated from a number of psychiatric disorders, particularly other anxiety disorders. Classically, panic attacks are characterized by their rapid onset developing within minutes and short duration, usually less than 10 to 15 minutes, in contrast to the anxiety associated with generalized anxiety disorder, which emerges and dissipates more slowly.

Neuronal circuits subserving fear are coexistent with that of anger. Both are thought to be mediated by dysfunctions in the medial part of temporal lobe and amygdala; but the circuitry responsible for the fear appears to be located lateral to the that of anger and rage. Destruction of the central part of the amygdaloid nucleus abolishes fear reaction. These nuclei are connected to lateral hypothalamus and midbrain tegmentum, the lesions of which can also evoke feeling of fear and anxiety.

Obsessive-Compulsive Disorder

Obsessions are recurrent, intrusive, senseless ideas, thoughts and images that are ego-dystonic and involuntary. Compulsions are repetitive activities carried out in response to an obsession and executed in a stereotyped and ritualized fashion. Lesions in basal ganglia orbitofrontal cortex and cingulate cortex are associated with obsessive-compulsive behavior.

Conditions affecting the basal ganglia and producing obsessive-compulsive disorder include Parkinson's disease, postencephalitic Parkinsonism ^{More Details}, Huntington's disease, progressive supranuclear palsy, tourette's disorder, neuroacanthocytosis, Sydenham's chorea, carbon monoxide poisoning, neonatal hypoxia, bilateral caudate infarctions, cardiopulmonary arrest and manganese poisoning. Obsessional thinking has also been observed in conjunction with neuroleptic-induced and postencephalitic oculogyric crises. Treatment of obsessions and compulsions in neurological disorders entails treatment of the underlying disease and symptomatic relief of the obsessive-compulsive disorder. [Table - 6] summarizes the various neurological disorders associated with obsessive-compulsive disorder.

Some evidence suggests an association between an immune reaction to streptococcal infections and either initial manifestations or dramatic exacerbation of OCD in children. This syndrome appears to emerge relatively acutely, in contrast to the more indolent onset of other cases of childhood OCD. Hence, in children with such presentations, the role of such an infectious process should be considered.

Finally, OCD is closely related to Tourette's disorder; the two conditions frequently co-occur, both in an individual over time and within families. In its classic form, Tourette's disorder is associated with a pattern of recurrent vocal and motor tics that bears only a slight resemblance to OCD. However, the premonitory urges that precede tics often bear a striking resemblance to obsessions and many of the more complicated motor tics can bear a close resemblance to compulsions.

Neurophysiology of OCD

In OCD, attention is riveted to a given thought or form of behavior which becomes overpowering as to control the patient's mind and behavior.

The neurobiological substrate for OCD and Tourette syndrome (TS) include both cortico-striato-thalamo- cortical circuits and the monoaminergic pathways that modulate activity in these pathways.[70] An aberrant orbitofrontal and limbic circuit has been postulated as the pathophysiological mechanism for OCD. Obsessions with aggressive and sexual theme as seen in TS have been related to a failure to inhibit the limbic circuits,[71] while counting obsessions and an obsessive need for symmetry and exactness have been attributed to failure to inhibit orbitofrontal circuit. The various cognitive and behavioral symptoms like obsessions, compulsions, impulsivity, coprolalia, echo-phenomena and self injurious behavior are found to be related to dysfunction of the orbitofrontal cortex, cingulate gyrus and caudate nucleus.[72] Involvement of the caudate nucleus may underlie the compulsive quality of tics. In OCD patients, signals from an over active orbitofrontal cortex may underscore feelings of fear and lead to ritualistic behavior, while the caudate nucleus and cingulate gyrus lesions are associated with the more visceral and affective aspects (associated with dread and worry) of the disorder. Some researchers believe that over activity along the cortico striatal- thalamo-cortical pathway may lead to the circuit becoming "stuck" resulting in escalating pattern of doubt and checking characteristics of many OCD patients. Higher rates of neurological soft signs are observed in patients with OCD.

Anterior cingulotomy and limbic leucotomy have been successfully used to treat the disabling ritualistic behavior in TS patients with OCD.[73] Similar benefit may be obtained by severing the frontothalamic connections between the orbitofrontal cortex to the dorsomedial nucleus of thalamus. Thus a limbic-basal ganglia-thalamo-cortical circuit has been postulated as the pathophysiological substrate for OCD.

The neurotransmitter implicated in the pathogenesis of OCD is serotonin. Drugs that are specific serotonin reuptake inhibitors are useful in this condition. The serotonin receptors are profoundly localized to the ventromedial caudate nucleus and the ventral striatum, which receive inputs from the orbitofrontal cortex and the anterior cingulate gyrus respectively.

Administration of serotonin antidepressants causes caudate disinhibition, thus enhancing the activity of the striopallidal thalamic circuit to damp the orbitothalamic overactivity. The improvement in OCD symptoms in patients with TS with dopamine receptor blocking drugs is related to the functional interaction between the brain serotonin and dopamine systems.

Altered Sexuality

Neurological disorders can produce alterations in sexual drive. Hypersexuality can occur in lesions of the medial temporal region, hypothalamus (tuberoinfundibular region), septal region as well as in orbitofrontal lesion. However, hypersexuality seen in frontal lobe lesions is different from that seen with temporal and hypothalamic lesions. Lesions of orbitofrontal lobe may remove the moral-ethical restraints and lead to indiscriminate sexual behavior.

Heightened sexual drive occurs in secondary mania, postictally (i.e., after a seizure), following markedly improved seizure control in patients with epilepsy (e.g., after temporal lobectomy or with improved anticonvulsant control of seizures), with introduction of levodopa or other dopaminergic agents in Parkinson's disease, with diencephalic or frontal lobe lesions, after septal injury and in the Kluver-Bucy syndrome. Hypersexuality has also been induced by amphetamines, cocaine, hyperthyroidism, hypercortisolism and androgen administration.

Markedly diminished sexual interest occurs with temporal lobe epilepsy, hypothalamic lesions and right hemisphere brain injuries. Superior frontal lesions are associated with a general loss of initiative that reduces all impulsivity including sexual.

Apathy and Akinetic Mutism (The Anterior Cingulate Syndrome)

Apathy is the absence or lack of feeling, emotion, interest, concern or motivation and has been reported frequently among patients with brain injury. Apathy is seen in patients with lesions of prefrontal lobe where there is associated indifference and psychomotor retardation. Similarly patients with anterior cingulate lesions may be apathetic and akinetic. Subcortical lesions can also produce apathy. Lesions in the internal globus pallidus and the posterior limb of the internal capsule have been reported to produce behavioral changes, such as motor neglect, psychic akinesia and akinetic mutism. The ansa lenticularis is one of the main internal pallidal outputs and it ends in the pedunculopontine nucleus after going through the posterior limb of the internal capsule. In rodents, this pathway has a prominent role in goal-oriented behavior and dysfunction of this system may explain the presence of apathy in patients with lesions of the posterior limb of the internal capsule.

Apathy is the most frequent neurobehavioral alteration seen in cerebral diseases particularly frontal lobes. There are fewer thoughts, fewer word uttered and fewer movements per unit time. They perceive and think more slowly, make fewer associations with a given idea, initiate speech less frequently and exhibit less interest. This type of extreme placidity is seen in lesions of bilateral cingulate gyri; but can also seen lesions of thalamus and septal region. Unlike the case in retarded depression, the mood is neutral. Patient is apathetic rather than depressed. Placcidity can also occur as a part of "Kluver- Bucy" syndrome, but the patient is more responsive to visual stimuli and they demonstrate hyperorality and hypersexuality.

Akinetic mutism (AM)[74] represents a wakeful state of profound apathy with indifference to pain, thirst or hunger and absence of motor or psychic initiative, manifested by lack of spontaneous movement, absent verbalization and failure to respond to questions or commands. The term abulia, derived from the Greek word "boul" or "will" refers to a similar but less severe psychomotor syndrome, encompassing lack of spontaneity, apathy and paucity of speech and movement.

Abulic patients are slow, make few extraneous movements and are generally aspontaneous. When you walk into the room, the abulic patient lies there, silent and motionless. He sees you enter, understands who you are, comprehends your questions, hesitates, seems to ignore you or gives yes-no answers to your questions. In some cases, abulia is extreme. Like bumps on a log, severely abulic patients do not speak unless spoken to; they do not move unless very hungry or ready to void. Even when ready to urinate, they may be incontinent because they are unable to energize themselves to go to the bathroom or do not care about the consequences of voiding in the bed or chair. In some patients, this apathy or aspontaneity is confused with depression, catatonia or laziness.[75]

The assessment of abulia begins with observation of spontaneous motor and verbal behavior. Secondly, delayed response to a question or command is another sensitive, although non-specific, indicator. When a patient with abulia is asked to count backwards from 20, they often do so only after repeated requests, reach 17 or 15 and stop without further prompting. Another simple bedside test for abulia is to have the patient say 'yes' every time you move your finger. Again, patients will correctly identify the first several movements and then cease responding.

The fact that similar abulia and akinetic syndrome can be seen in lesions of caudate, globus pallidus suggests that lesion anywhere in the frontal-subcortical circuits can produce such deficits. Akinetic mutism has been described with craniopharyngiomas, obstructive hydrocephalus, tumors in the region of the third ventricle and other conditions involving the ventral striatum (nucleus accumbens and ventromedial caudate), ventral globus pallidus and medial thalamus. Unilateral lesions of the anterior cingulate (AC) cortex produce transient AM[76] while the most dramatic examples of AM follow bilateral AC lesions.

Emotional Lability

Patients with orbitofrontal lesions are emotionally labile and even minor stimuli will produce exaggerated response. Affect is out of proportion to what should normally be there for that particular stimulus. However the affect is congruous with the visceral and motor components of behavior. This type of emotional lability is seen with bifrontal disease.

This should be differentiated from the emotional incontinence seen in pseudobulbar palsy and shallow facetiousness (witzelschut). In witzelschut, patient is inappropriately humorous about serious subjects. In emotional incontinence a slightest provocation may throw the patient into stereotyped spasm of laughter or uncontrollable spasm of crying. Here the affect is same as in any other person, but the outward expression of emotion in the form of crying and laughing is excessive and uncontrollable.

Right hemisphere lesions often show undue cheerfulness and indifferent emotional reactions (anosodiaphoria). An emotional valence hypothesis proposes that the right hemisphere processes negative emotions and the left hemisphere, positive emotions. Vascular lesions in the left anterior cortex are found to be associated with a significantly higher frequency of major depression than lesions in other locations. Left-side lesions are commonly associated with akinesia and depression, whereas right side lesions are more often associated with euphoria and underestimation by patients of the seriousness of the illnesses.

Temporolimbic lesions especially tumours tend to produce psychosis and schizophrenia like illness, perhaps because of disruption of limbic structures, including components of papez circiut.

Fugue States

Fugue states refers to periods of amnesia associated with wandering tendency and can occur in organic (temporal lobe epilepsy) or psychiatric causes.

Epileptic fugue states are brief and patient does not retain contact with environment. However, patients with complex partial seizures, typical or atypical absences may present with prolonged confusional states due to complex partial status epilepticus or absence status. Such attacks may be the first manifestation of the seizure disorder or occur in the setting of known epilepsy and cause confusion with primary psychiatric causes.

A fugue state may arise without an organic physical cause, as a conversion symptom. These episodes may be brief or very prolonged, lasting for days or even weeks. If seen, at the time of an episode inconsistencies are often found on examination of the mental state and an EEG will be unremarkable. If related to psychiatric disability such as depression, it is usually seen in the setting of escape from difficult or intolerable circumstances. Unlike epileptic automatism, which is briefer, patient remains in contact with environment, manipulates it successfully and appropriately and often draws much attention to him from others.

The diagnosis is more difficult if the patient is only seen after the event. The matching of witness's accounts and the apparent sequence of events is essential, but it may remain difficult to come to a firm conclusion.

Organic Catatonic Disorder

Catatonia has been reported to occur in patients with diverse toxic, neurologic and infectious conditions. Encephalitis and carbon monoxide poisoning are presumed to be the most common causes of the syndrome.[77] Other reported etiologies of organic catatonia include ecstasy intoxication,[78] cerebral lupus and hydrocephalus,[79] hereditary cerebellar ataxia,[80] multiple sclerosis and vitamin B12 deficiency.[81] Waxy flexibility has been reported in contralateral parietal lesions.[82] In a case series, Swartz et al[83] reported that catatonia due to chronic neurologic conditions does not respond as reliably to electroconvulsive therapy (ECT) and lorazepam as functional catatonia does.