Callosal warning syndrome.

OBJECTIVE: To report the clinical and imaging findings in a patient with an initial fluctuating disconnection syndrome due to corpus callosal ischemia that ultimately culminated in infarction with persistent symptoms. CASE REPORT: A 40-year-old, hypertensive, right-handed man presented with transient, stereotyped symptoms of corpus callosal disconnection (intermanual conflict, apraxia, dysgraphia and construction difficulties in his left hand). Serial magnetic resonance imaging scans demonstrated the ischemic nature of the initial fluctuating symptoms and later showed callosal infarction when the symptoms were persistent. Magnetic resonance angiogram did not reveal significant stenosis or occlusion of the internal carotid or proximal portion of anterior cerebral arteries. Patient received standard treatment for ischemic stroke and at follow-up 1 month later, had mild left hand apraxia, dysgraphia and construction difficulties. CONCLUSION: The case highlights the unusual occurrence of crescendo transient ischemic attacks culminating in infarction in the location of corpus callosum. We have termed this novel stroke syndrome as 'callosal warning syndrome' as the temporal profile was quite indistinguishable from that of relatively well-known stroke warning syndromes in the location of internal capsule and pontine tegmentum.

Wilson's disease: a clinico-neuropathological autopsy study.

Wilson's disease (WD), a familial neurological disorder involving the brain and liver secondary to altered copper metabolism, is common in South India. In view of the paucity of studies on this condition, the pathomorphological features of eight cases of WD were studied in detail at autopsy (brain alone, 1; brain and liver biopsy, 1; brain and visceral organs, 6), and are described with a discussion of the differential features of the neurological and hepatic forms. Of the six patients presenting with neurological manifestations, five had central pontine myelinolysis, five had subcortical white matter cavitations, four had putaminal softening, and six had variable ventricular dilatation, unlike the hepatic form. The presence of Opalski cells and pontine myelinolysis appear to be specific to the neurological form of WD. Liver abnormalities were observed in all cases (cirrhosis, 6; steatosis, 4; chronic active hepatitis, 2). Contrary to the rubric 'hepatolenticular degeneration', involvement of the lenticular nucleus was not universal, and nor was the pathology restricted to these anatomical areas.

Hypertrophic cranial pachymeningitis in countries endemic for tuberculosis: diagnostic and therapeutic dilemmas.

Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder with few studies correlating clinical, imaging and histopathological features. The aim of this study was to describe clinical and laboratory observations and therapeutic options of patients with HCP. Eleven patients with HCP (M:F 6:5; age range, 23-52 years) were evaluated over 10 years. Etiology was ascertained by MRI and laboratory tests and confirmed by biopsy of meninges and/or brain (7), nasal mucosa (1), mediastinal lymph node (1), muscle (2) or conjunctiva (2). Salient clinical features were headache (7), multiple cranial neuropathies (8), visual disturbances (6), seizures (2) and hemiparesis (2). Abnormal tests included: rapid erythrocyte sedimentation rate (3), positive serum venereal disease testing (1), chest CT abnormalities (4/6) and positive Mantoux test (2/5). Cerebrospinal fluid changes (10/11) revealed the following: cell count 0-47/mm(3); protein 14-95 mg/mL; and glucose of 44-79 mg/mL. Contrast MRI revealed a variable extent of thickened dura mater in all patients. Histopathology (n=11) confirmed chronic inflammation (100%) and provided specific etiology in six (vasculitis [2], sarcoidosis [2], tuberculosis [1], Wegener's granulomatosis [1]). Treatment included steroids only (4), anti-tubercular therapy with steroids (5), penicillin (1) and cyclophosphamide and plasmapheresis (1). During follow-up (27.0+/-26.3 months) there was significant recovery (9/9). On serial imaging (4), the lesion remained the same in three and resolved partially in one patient. HCP, despite frequently posing diagnostic and therapeutic challenges, has favorable outcome when treated appropriately.

Psychiatric manifestations in Wilson's disease: a cross-sectional analysis.

Behavioral and psychiatric abnormalities in Wilson's disease (WD) have a variable frequency and spectrum. This study involved evaluation of the psychiatric comorbidities in patients of Wilson's disease, using structured clinical interview for DSM-IV Axis-I disorders (SCID). Among the 50 confirmed patients with Wilson's disease recruited for this study, 12 patients (24%) fulfilled the diagnostic criteria for syndromic psychiatric diagnosis: bipolar affective disorder (18%), major depression (4%), and dysthymia (2%). Formal assessment of psychopathology in all patients with Wilson's disease may have therapeutic significance.

Quality of life in Wilson's disease.

BACKGROUND: Assessment of Quality of life (QoL) is fast assuming significance as the measure of health in many disorders. AIM: To correlate clinical severity and QoL in patients with Wilson's disease (WD). MATERIALS AND METHODS: We evaluated patients of WD on regular follow up for at least two years and aged over 18 years using Neurological Symptom Score (NSS) for clinical severity and WHO-BREF for QoL at a university teaching hospital. Patients with inability to respond to the questionnaire due to behavioral problems, low IQ or other disease related factors were excluded. These 30 patients (M:F:: 23:7) had a mean age of 27.97 +/- 11.16 years at evaluation and the mean duration of treatment of 9.2 +/- 6.4 years. RESULTS: All four domains of WHO-QoL-BREF viz., Physical, Psychological, Social and Environmental correlated well with each other (p < 0.01). The NSS correlated inversely with the physical domain (p < 0.02), while the duration of treatment had a positive correlation with the physical domain (p < 0.01). None of the other features of QoL showed any significant correlation with age, NSS or duration of treatment. CONCLUSION: QoL is complementary to formal neurological assessment and should be routinely incorporated in the evaluation of outcome of patients with WD and other chronic neurological disorders.

Dominant psychiatric manifestations in Wilson's disease: a diagnostic and therapeutic challenge!

INTRODUCTION: Recognition of psychiatric manifestations of Wilson's disease (WD) has diagnostic and therapeutic implications. OBJECTIVE: To describe the clinical features and psychopathology of patients with WD who had initial or predominant psychiatric manifestations. PATIENT AND METHODS: Records of 15 patients with WD (M:F: 11:4), from a large cohort of 350 patients, with predominant psychiatric manifestations at onset were reviewed. Their initial diagnosis, demographic profile, family history, pre-morbid personality, clinical manifestations, treatment and outcome were recorded. RESULTS: Their mean age at diagnosis was 19.8+/-5.8 years. Six patients were born to consanguineous parentage and two patients each had family history of WD and past history of psychiatric illness. Diagnosis of WD was suspected by detection of KF rings (all), observing sensitivity to neuroleptics (n=2), history of jaundice (n=2) and family history suggestive of WD (n=9). Psychiatric manifestations could be classified as affective disorder spectrum (n=11) and schizophreniform-illness (n=3). While the psychiatric symptoms improved in five patients with de-coppering therapy, seven patients needed symptomatic treatment as well. Three of the four patients who responded to de-coppering therapy were sensitive to neuroleptics. Long-term follow up of 10 patients revealed variable recovery. CONCLUSIONS: Young patient with psychiatric manifestations with clues like history of jaundice, family history of neuropsychiatric manifestations and sensitivity to neuroleptics should be evaluated for WD to avoid delay in diagnosis and associated morbidity. SIGNIFICANT OUTCOMES: The study reemphasizes the importance of behavioral manifestations in Wilson disease in terms of diagnosis and management difficulties. LIMITATIONS: Retrospective nature of the study.

Dysmyelinating neuropathy in benign form of megalencephalic leukoencephalopathy with subcortical cysts: a novel observation from south India.

A 37-year-old gentleman presented with macrocephaly since early childhood and progressive impairment of motor and cognitive functions. Magnetic resonance imaging revealed extensive white matter involvement and frontotemporal subcortical cysts. Absent ankle jerk and abnormal nerve conduction study raised a possibility of associated peripheral neuropathy. Sural nerve biopsy was suggestive of dysmyelinating neuropathy. This report serves to expand the clinical spectrum of this rare leukodystrophy.

Sequential MRI changes in Wilson's disease with de-coppering therapy: a study of 50 patients.

Wilson's disease (WD) is clinically and radiologically a dynamic disorder. However, there is a paucity of studies involving sequential MRI changes in this disease with or without therapy This study looked at serial MRI changes and their clinical correlate in patients with WD The severity of MRI changes using 1.5 T MRI in 50 patients with WD was graded based on alteration in signal intensity of focal lesions and atrophy. Details of clinical manifestations, Schwab and England Activities of daily living (MSEADL) score, Neurological Symptom Score (NSS) and Chu staging were recorded. Clinical severity and disability scores were correlated with MRI scores using SPSS v10 The mean age at onset of illness and diagnosis was 12.8+/-5.6 years and 14.4+/-6.0 years, respectively. At the time of first MRI, patients had been treated for 49.0+/-77.3 months. At a follow-up of 24.2+/-12.2 months, clinically 36 patients had improved, 9 remained the same and 5 had worsened. Serial imaging revealed an improvement in MRI parameters in 35 patients, no significant changes in 10, worsening in 4 and an admixture of resolving and evolving changes in 1. The overall MRI score improved from 8.2+/-5.7 to 5.9+/-6.6. There was an improvement in measures of disability and impairment in all: Chu stage, 11.5+/-0.7 to 1.3+/-0.6; MSEADL score (%), 79.7+/-27.6 to 88.0+/-25.4; NSS, 10.6+/-11.2 to 8.0+/-11.6, with good clinico-radiological correlation. Patients with extensive changes, white-matter involvement and severe diffuse atrophy had a poor prognosis In conclusion, the majority of patients with WD showed variable improvement in clinical and MRI features when treated.

Extensive cortical magnetic resonance signal change in proximal urea cycle disorder.

The authors report a 3-year 8-month-old girl presenting with episodic hyperammonemic encephalopathy probably due to a proximal urea cycle disorder. The magnetic resonance imaging (MRI) of the brain performed during the third episode revealed extensive and diffuse cerebral cortical signal changes with sparing of occipital cortex. It is believed that intracerebral accumulation of glutamine mainly in astrocytes is the major cause of the encephalopathy. This results in astrocyte swelling, brain edema, intracranial hypertension, and cerebral hypoperfusion.

Menkes syndrome presenting as myoclonic seizures: neuroimaging and EEG observations.

The authors report an 11-month-old boy with Menkes kinky hair disease who presented with global delay in acquiring milestones and repeated myoclonic jerks. He had scanty, hypopigmented scalp hairs with steely wool-like texture and intervening zones of alopecia. There was low serum ceruloplasmin (5 mg/dL) and copper (24.2 microg/dL). Neuroimaging of the brain revealed marked cerebral atrophy and significant delayed myelination. Magnetic resonance angiography showed tortuous cerebral and neck blood vessels. There was poor therapeutic response to symptomatic treatment.

Wilson disease: description of 282 patients evaluated over 3 decades.

The clinical manifestations of Wilson disease (WD) are varied and challenging. We conducted the current study to present the phenotypic characteristics and follow-up for a large cohort of patients with WD. We reviewed the medical records of 282 cases of WD (male:female ratio, 196:86) for clinical features, investigations, treatment, and outcome data. The clinical presentations were as follows: hepatic, 42 (14.9%); hepato-neurologic, 10 (3.5%); neurologic, 195 (69.1%); pure psychiatric, 7 (2.4%); osseomuscular, 6 (2.1%); and "presymptomatic," 15 (5.3%). Mean age was 15.9 years. Presymptomatic patients and those with the hepatic form of WD were younger and patients with osseomuscular and psychiatric forms were older than neurologic patients. The mean duration of illness at the time of diagnosis was 28 months. Predominant neurologic features were as follows: parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%; chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16%. Kayser-Fleischer (KF) rings were seen as follows: neurologic patients, 100%; hepatic patients, 86%; and presymptomatic patients, 59%. Positive family history was noted in 47% and consanguinity in 54%. Patients born of consanguineous parents had an earlier age of onset and shorter duration of illness before presentation. Serum ceruloplasmin was decreased in 93% and 24-hour urinary copper excretion was increased in 70% of patients. Neuroimaging (computed tomography/magnetic resonance imaging) and electrophysiologic abnormalities were seen in many patients. Overall, 195 patients were on D-penicillamine therapy and 182 on zinc sulphate. Follow-up data, available for 225 patients, for a mean duration of 46 months, revealed improvement in 176, no change in 20, and deterioration in 6. Twenty-three patients died. To conclude, despite increased awareness and recognition and significant inroads into therapeutic frontiers, follow-up remains poor in developing countries and a return to previous level of functioning is not universal.

Hepatic myelopathy: a rare complication following extrahepatic portal vein occlusion and lienorenal shunt.

A 19-year-old gentleman presented with slowly progressive spastic paraparesis, 2 years after the therapeutic lienorenal shunt for portal hypertension secondary to cirrhosis and portal vein occlusion. After 2 years of initial evaluation, the motor functions had not worsened further. He did not have any obvious clinical or EEG features of hepatic encephalopathy. Other causes for myelopathy were ruled out. Contribution of portal vein occlusion to portosystemic shunting has not been reported previously in patients with 'hepatic myelopathy.' This uncommon complication needs to be considered in patients with shunt surgery for relieving portal hypertension.

Wilson's disease: cranial MRI observations and clinical correlation.

INTRODUCTION: Study of MRI changes may be useful in diagnosis, prognosis and better understanding of the pathophysiology of Wilson's disease (WD). We aimed to describe and correlate the MRI abnormalities of the brain with clinical features in WD. METHODS: MRI evaluation was carried out in 100 patients (57 males, 43 females; mean age 19.3+/-8.9 years) using standard protocols. All but 18 patients were on de-coppering agents. Their history, clinical manifestations and scores for severity of disease were noted. RESULTS: The mean duration of illness and treatment were 8.3+/-10.8 years and 7.5+/-7.1 years respectively. MRI of the brain was abnormal in all the 93 symptomatic patients. The most conspicuous observations were atrophy of the cerebrum (70%), brainstem (66%) and cerebellum (52%). Signal abnormalities were also noted: putamen (72%), caudate (61%), thalami (58%), midbrain (49%), pons (20%), cerebral white matter (25%), cortex (9%), medulla (12%) and cerebellum (10%). The characteristic T2-W globus pallidal hypointensity (34%), "Face of giant panda" sign (12%), T1-W striatal hyperintensity (6%), central pontine myelinosis (7%), and bright claustral sign (4%) were also detected. MRI changes correlated with disease severity scores (P<0.001) but did not correlate with the duration of illness. CONCLUSION: MRI changes were universal but diverse and involved almost all the structures of the brain in symptomatic patients. A fair correlation between MRI observations and various clinical features provides an explanation for the protean manifestations of the disease.

Adult onset subacute sclerosing panencephalitis: clinical profile of 39 patients from a tertiary care centre.

Clinical and laboratory characteristics of 39 patients with adult onset subacute sclerosing panencephalitis (SSPE) are described and compared to those of juvenile onset patients regarding preceding measles, age at onset, gender, interval between onset and diagnosis, clinical profile, and course during follow up. Diagnosis was based on clinical and electroencephalographic findings and raised anti-measles antibody titres in cerebrospinal fluid. Mean age at SSPE symptom onset was 20.9+/-4.9 years and mean interval from onset to diagnosis was 6.3+/-9.6 months. Referral diagnosis was accurate in only 12 patients. Presenting symptoms included myoclonus, behavioural changes, seizures, and cognitive, visual, and extrapyramidal disturbance. All patients received symptomatic therapy; 19 also received disease modifying agents. Five of seven pregnant women had successful deliveries. The follow-up period varied widely (maximum 60 months, median 9 months). The profile of adult onset SSPE did not differ from the rest of the cohort, except for a longer interval between measles infection and symptom onset (p<0.0001). SSPE in adults poses diagnostic challenges for clinicians. A high index of suspicion and appropriate investigations are necessary for early diagnosis and counselling.

Neurological manifestations of Ehlers-Danlos Syndrome.

Ehlers-Danlos Syndrome (EDS) is more identified for its cutaneous features but its neurological manifestations have not received the focused attention. Four patients of Ehlers-Danlos Syndrome (EDS) with neurological manifestations were evaluated for phenotypic data. These four men were from three families and two had consanguineous parentage. The mean age at onset and presentation of neurological symptoms were 10.5 years and 19 years respectively. Patient 1 presented with bilateral optic atrophy, sensorineural deafness, cerebellar ataxia and neuropathy. Patient 2 had marfanoid habitus, chorea and cerebellar ataxia. Patient 3 had action and percussion myotonia, wasting and weakness of sternocleidomastoid and distal limb muscles. Patient 4 had action myotonia, mirror movements of both hands and neuropathy. MRI of brain showed right parietal polymicrogyria. Neuroaxis involvement at multiple levels in EDS may have prognostic significance.