Sanjib Sinha

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

INTRODUCTION Recognition of psychiatric manifestations of Wilsons 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.

Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's disease.

BACKGROUND There are only a few reports regarding the fertility and outcome of pregnancy in Wilsons disease (WD) and none from India. The authors in this study discuss various aspects of fertility in 16 women with WD. METHODS Retrospective analysis of data from a large cohort of WD, being followed at a tertiary care center. RESULTS Sixteen patients had conceived on 59 occasions with 30 successful pregnancies, 24 spontaneous abortions, 2 medical terminations of pregnancy and 3 still births. Diagnosis of WD was established after conception in 10 presymptomatic patients while six patients were already on treatment. Among these 16 patients, 9 had history of spontaneous abortions and 12 had successful pregnancies. None of the clinical features of WD changed during pregnancy, with or without treatment. All the 30 babies were full-term and delivered healthy. CONCLUSION Recurrent abortions are common especially in women with untreated Wilsons disease. However, successful pregnancies and uneventful full-term delivery may occur in mothers of WD on treatment and in undiagnosed, undetected presymptomatic patients. Pregnancy does not seem to have adverse effect on the clinical course of Wilsons disease. Teratogenecity was not seen in the present series with low-dose penicillamine and zinc sulphate.

Modulation of cardiac autonomic balance with adjuvant yoga therapy in patients with refractory epilepsy

The practice of yoga regulates body physiology through control of posture, breathing, and meditation. Effects of yoga on autonomic functions of patients with refractory epilepsy, as quantified by standardized autonomic function tests (AFTs), were determined. The yoga group (n=18) received supervised training in yoga, and the exercise group (n=16) practiced simple routine exercises. AFTs were repeated after 10 weeks of daily sessions. Data were compared with those of healthy volunteers (n=142). The yoga group showed significant improvement in parasympathetic parameters and a decrease in seizure frequency scores. There was no improvement in blood pressure parameters in either group. Two patients in the yoga group achieved normal autonomic functions at the end of 10 weeks of therapy, whereas there were no changes in the exercise group. The data suggest that yoga may have a role as an adjuvant therapy in the management of autonomic dysfunction in patients with refractory epilepsy.

Epilepsia Partialis Continua over last 14 years: experience from a tertiary care center from south India.

Epilepsia Partialis Continua (EPC), a subtype of status epilepticus has varied etiology and the outcome depends on the cause. The aim of this study was to analyze the demographic, semiology, etiology, radiological findings, therapeutic response and outcome of EPC. This is a retrospective analysis of 76 patients (M:F: 46:30; mean age: 30.2+/-23.4 years; median age: 26 years) evaluated at our center over last 14 years. Twenty-three subjects (30.3%) had epilepsy for a mean of 25.8+/-52.3 months (range: 1-81 years; median: 14) before developing EPC and in half of them, seizures were controlled with anti-epileptic drugs (AEDs). Rest 53 (69.3%) manifested as de novo. The mean duration of EPC was 47.02+/-188.2 days (range: 1h to 48 months; median: 3 days). One patient of generalized convulsive SE (GCSE) evolved into EPC while five patients of EPC evolved into GCSE. CT scan of brain (n-76) was abnormal in 53 (69.7%) while all the 11 MRI scans which were available were abnormal. EEG (n-21) was abnormal in all but one, however it was non-specific in 7. The diagnoses were-idiopathic: 17, ischemic stroke: 15, meningo-encephalitis: 8, Rasmussens encephalitis (RE): 7, granuloma: 6, diabetic-non-ketotic-hyperosmolar-coma (DNKHC): 6, CNS malignancies (primary/secondary): 4, birth injury: 4, cerebral venous thrombosis: 3, CNS tuberculosis: 2, and cerebritis, HIV-related, toxemia of pregnancy, and MERRF one each. Patients of >40 years (n=21) had stroke (10), idiopathic (6), DNKHC (4) and metastasis (1) as common causes. Only 12 of them received single AED, while others required 2 or more AEDs to control the seizures. The outcome (n=72) was-controlled: 43 (59.7%); uncontrolled: 26 (36.1%) (RE: 7, idiopathic: 5, birth injury: 4, encephalitis: 3, malignancy: 2, granuloma and MERRF: 1 each) and three patients succumbed (encephalitis: 2, idiopathic: 1). Causes of EPC are varied and it depends on age. Underlying cause determined the outcome and could be refractory in RE, idiopathic, and when associated with birth injury, malignancy and encephalitis. Treatment of underlying cause is essential in addition to AEDs.

Seizures in HIV-seropositive individuals : NIMHANS experience and review

Seizures are not uncommon in patients with human immunodeficiency virus (HIV) infection, and with the upsurge in HIV infection this may be an important cause for acute symptomatic seizures. Seizures may rarely be the presenting manifestation of HIV infection. Opportunistic infections such as toxoplasmosis, tuberculosis, progressive multifocal leucoencephalopathy (PML), cryptococcal meningitis and polymicrobial infections, metabolic and electrolyte disturbances, and drugs are common causes of new‐onset seizures in HIV‐seropositive individuals. In the absence of any cause, primary HIV infection may be considered responsible for seizures. Because seizures tend to recur in and because they are a poor prognostic indicator in HIV infection, treatment with antiepileptic drugs (AEDs) is the norm. The treatment of HIV‐infected individuals with seizures comprises of the administration of AEDs, specific treatment of the underlying conditions, and antiretroviral drugs. Clinicians must consider both therapy‐compromising drug–drug and drug–disease interactions while choosing appropriate AEDs. The ideal AED in this setting is one that does not affect viral replication, have limited protein binding, and have no effects on the hepatic cytochrome P450 enzyme system. The risks for AED‐induced allergic skin rash appears to be high in HIV‐seropositive individuals.

Sleep disturbances in juvenile myoclonic epilepsy: A sleep questionnaire-based study

Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age- and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F=22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure- or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification.

Cranial MRI in Acute Hyperammonemic Encephalopathy

Cranial magnetic resonance imaging was performed in three cases of acute hyperammonemic encephalopathy with three diverse etiologies: infantile citrullinemia, acute hepatic encephalopathy, and proximal urea cycle disorder. All three patients exhibited diffuse extensive cortical signal changes and swelling. Neurologic outcome was poor in all three cases. Knowledge of the magnetic resonance imaging findings of hyperammonemic encephalopathy may help in early diagnosis and treatment and could influence the neurologic outcome.

Sleep-related disorders among a healthy population in South India

INTRODUCTION Sleep-related disorders (SRDs) though frequent, are under-reported and their implications are often neglected. OBJECTIVE To estimate SRDs in an apparently healthy South Indian population. MATERIALS AND METHODS Data was collected by administering a questionnaire including Sleep Disorders Proforma, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index (PSQI) to 1050 apparently healthy attendants/relatives of patients attending a tertiary healthcare institution. RESULTS The mean age of the respondents was 35.1±8.7 years with even gender distribution (male: female; 29:21), work hours were 7.8±1.33 h and had regional representation from the southern Indian states. The majority of the respondents did not report any significant medical/psychiatric co-morbidities, hypertension was noted in 42.6%, in one-fourth, the body mass index (BMI) was >25, and in 7.7% the neck size was >40 cm. Daily tea (70.3%) and coffee (17.9%) consumption was common and 22.2% used tobacco. Average time-to-fall-asleep was 22 min (range: 5-90 min), average duration-of-actual-sleep was 7 h (range: 3.5-9.1 h) with the majority (93.8%) reporting good-quality sleep (global PSQI ≤5). The reported rates of SRDs varied between 20.0% and 34.2% depending on the instrument used in the questionnaire. Insomnia, sleep-related breathing disorders (SRBD), narcolepsy, and restless legs syndrome (RLS) were reported by 18.6%, 18.4%, 1.04% and 2.9%, respectively. Obesity was not strongly associated with SRBD. in 51.8% of subjects with SRBD BMI was <25 kg/m 2 . Of the respondents with insomnia, 18% had difficulty in initiating sleep, 18% in maintaining sleep and 7.9% had early morning awakening. Respondents attributed insomnia to depression (11.7%) or anxiety (2.5%). Insomnia was marginally high in females when compared to males (10.3% vs. 8.3%) and depression was the major reason. RLS, which was maximal at night, was responsible for delayed sleep onset (74.2%). Other SRDs included night terrors (0.6%), nightmares (1.5%), somnambulism (0.6%), and sleep-talking (2.6%). Family history of SRDs was present in 31.4% respondents. While, only 2.2% of the respondents self-reported and acknowledged having SRD, health-seeking was extremely low (0.3%). CONCLUSION SRDs are widely prevalent in India. Considering the health implications and poor awareness, there is a need to sensitize physicians and increase awareness among the public.

Symptomatic seizures in neurosyphilis: An experience from a University Hospital in south India

PURPOSE Neurosyphilis has protean clinical manifestations, including epilepsy. However, there is paucity of literature providing details regarding seizures. The aim of the study was to analyze the clinical profile and brain imaging features of 30 patients of neurosyphilis, and to evaluate the predictors and the outcome of seizures in this subgroup. PATIENT AND METHODS Among the 119 patients (M:F:: 84:35) of neurosyphilis, evaluated over 6 years, 30 patients (M:W::23:7, age: 37.5+/-10.1 years, duration of illness: 11.9+/-20.1 months) were reported to have seizures. CSF-VDRL was positive in all. In addition, HIV serology was positive in 2/20. RESULTS Seizure was the dominant symptom in all and lone manifestation in two patients. None had history of epilepsy. Their seizure profile was: generalized (17), partial (8), and status epilepticus (5). Concomitant manifestations were encephalopathy (7), meningitis (7), dementia (6), behavioral disturbances (4), stroke (2), and optic atrophy (1). CSF study revealed pleocytosis in 24 (34.6+/-51.5/cu mm) and raised protein in 20 (67+/-33.3mg%). CT scan was abnormal in 26 patients and revealed diffuse atrophy in all and focal hypodensities in 5 patients. MRI of brain (6) showed features of ischemia (2), meningeal enhancement (1) and white matter (1) and medial temporal (2) signal changes. Three patients had reversible periodic lateralized epileptiform discharges (PLEDs), without structural lesion. Nineteen patients received penicillin and/or ceftriaxone. At a mean follow up of 6.7+/-9.4 months, 13/17 had variable improvement. Nine patients required polytherapy and seizures remained uncontrolled in five patients. CONCLUSIONS Symptomatic seizures due to neurosyphilis are frequent, may have diverse underlying mechanism(s) and rarely can be the lone manifestation. In view of availability of specific therapy for syphilis, a high index of suspicion is recommended.

Progressive myoclonic epilepsy: A clinical, electrophysiological and pathological study from South India

Progressive myoclonic epilepsy (PME) is a syndrome complex encompassing different diagnostic entities and often cause problems in diagnosis. We describe the clinical, electrophysiological and pathological features of 97 patients with the diagnosis of PME evaluated over 25 years. Case records of confirmed patients of Neuronal ceroid lipofuscinosis (NCL = 40), Lafora body disease (LBD = 38), Myoclonic epilepsy with ragged red fibers (MERRF = 10), and probable Unverricht-Lundberg disease (ULD = 9) were reviewed. The mean age at onset in patients with NCL (n = 40) was 5.9+/-9.1 years (M:F:: 28:12). Subtypes of NCL were: late infantile (n = 19), infantile (n = 8), juvenile (n = 11) and adult (n = 2) NCL. EEG (n = 37) showed varying degree of diffuse slowing of background activity in 94.6% and epileptiform discharges in 81.1% of patients. Slow frequency photic stimulation evoked photo-convulsive response in 5 patients only. Giant SSEP was demonstrated in 7 and VEP study revealed a prolonged P100 (2) and absent waveform (7). Electrophysiological features of neuropathy were present in 3 patients. Presence of PAS and Luxol Fast Blue (LFB) positive, auto fluorescent (AF) ceroid material in brain tissue (n = 12) and electron microscopy of brain (n = 5), skin (n = 28) and muscle (n = 1) samples showing curvilinear and lamellar bodies established the diagnosis. Patients of LBD (mean age of onset at 14.4+/-3.9 years, M:F:: 24:14) with triad of PME symptoms were evaluated. EEG (n = 37) showed variable slowing of background activity in 94.6% and epileptiform discharges in 97.4%. Photosensitivity with fast frequency was observed only in 5 patients. CT (n = 32) and MRI (n = 4) revealed diffuse cortical atrophy. Giant SSEP was demonstrated in 24 patients of LBD while VEP study revealed a prolonged P100 (4) and absent waveform (8). Electrophysiological features of neuropathy were present in one patient. Diagnosis was established by the presence of PAS positive diastase resistant, Lugols Iodine labeled inclusions in sweat glands of axillary skin (n = 35), brain (n = 2) and liver (n = 1). Ten patients with MERRF (mean age at onset: 14.6+/-5.8 years; M: F:: 3:2) had triad of PME symptoms. Muscle biopsy revealed oxidative reaction product and classical ragged red fibers. In nine patients of PME without cognitive decline, probable diagnosis of ULD (mean age at onset: 13.8+/-9.5 years) was considered after biopsy of skin and/or muscle excluded other forms of PMEs. Neuronal ceroid lipofuscinosis and Lafora body diseases were the common causes of PME in the series from south India. This is one of the largest series from the Indian subcontinent to the best of our knowledge. Photosensitivity is notably less common in LBD/NCL in this series distinctly different from those reported in the literature. Further exploration is required to determine whether different genotype is responsible. Morphological changes were helpful in diagnosis and could be confirmed by biopsy of peripheral tissues like skin and muscle in majority (60%). Electron microscopy was helpful in the diagnosis NCL and MERRF.