Madhu Nagappa

Neurosyphilis: MRI features and their phenotypic correlation in a cohort of 35 patients from a tertiary care university hospital

IntroductionThe clinical and MR imaging features of neurosyphilis are highly varied. In this study, we describe the spectrum of the imaging findings in patients with neurosyphilis.MethodsThe MR imaging observations of 35 patients diagnosed to have neurosyphilis on the basis of cerebrospinal fluid reactive for the Venereal Disease Research Laboratory test were reviewed.ResultsAll the 35 patients, including four with human immunodeficiency virus coinfection, met the CDC diagnostic criteria for neurosyphilis. Patients were classified into three groups: (1) neuropsychiatric, (2) meningovascular, and (3) myelopathic, based on the dominant clinical manifestations. Fourteen patients with neuropsychiatric manifestations showed diffuse cerebral atrophy (14), parenchymal signal changes in the mesial temporal region (2) and temporal and basifrontal regions (1), infarcts (3), and nonspecific white matter changes (3). Eleven patients with meningovascular form showed infarcts (6), diffuse cerebral atrophy (3), signal changes in the mesial temporal region (3), sulcal exudates (1), progressive multifocal leukoencephalopathy (1), and a mass surrounding the carotid sheath (1). Spine imaging in ten patients with myelopathy showed long-segment signal changes (5), contrast enhancement (2), and dorsal column involvement (2). Three of these patients had normal spinal study. Six patients in the myelopathic group also underwent brain MRI that showed signal changes in the temporal region (2) and frontal region (1), multiple infarcts (1), and enhancing hypothalami (1). Three patients had normal study.ConclusionMRI abnormalities in neurosyphilis are protean and mimic of many other neurological disorders and thus require a high index of suspicion to reduce diagnostic omissions.

Tumefactive demyelination: clinical, imaging and follow-up observations in thirty-nine patients

We describe the clinical, neuroimaging and pathological features and therapeutic outcome in a large cohort of 39 patients with tumefactive demyelination.

Magnetic resonance imaging correlates of genetically characterized patients with mitochondrial disorders: A study from south India

BACKGROUND Large studies analyzing magnetic resonance imaging correlates in different genotypes of mitochondrial disorders are far and few. This study sought to analyze the pattern of magnetic resonance imaging findings in a cohort of genetically characterized patients with mitochondrial disorders. METHODS The study cohort included 33 patients (age range 18 months-50 years, M:F - 0.9:1) with definite mitochondrial disorders seen over a period of 8 yrs. (2006-2013). Their MR imaging findings were analyzed retrospectively. RESULTS The patients were classified into three groups according to the genotype, Mitochondrial point mutations and deletions (n=21), SURF1 mutations (n=7) and POLG1 (n=5). The major findings included cerebellar atrophy (51.4%), cerebral atrophy (24.2%), signal changes in basal ganglia (45.7%), brainstem (34.2%) & white matter (18.1%) and stroke like lesions (25.7%). Spinal cord imaging showed signal changes in 4/6 patients. Analysis of the special sequences revealed, basal ganglia mineralization (7/22), lactate peak on magnetic resonance spectrometry (10/15), and diffusion restriction (6/22). Follow-up images in six patients showed that the findings are dynamic. Comparison of the magnetic resonance imaging findings in the three groups showed that cerebral atrophy and cerebellar atrophy, cortical signal changes and basal ganglia mineralization were seen mostly in patients with mitochondrial mutation. Brainstem signal changes with or without striatal lesions were characteristically noted in SURF1 group. There was no consistent imaging pattern in POLG1 group. CONCLUSION Magnetic resonance imaging findings in mitochondrial disorders are heterogeneous. Definite differences were noted in the frequency of anatomical involvement in the three groups. Familiarity with the imaging findings in different genotypes of mitochondrial disorders along with careful analysis of the family history, clinical presentation, biochemical findings, histochemical and structural analysis will help the physician for targeted metabolic and genetic testing.

Bilateral hypertrophic olivary nucleus degeneration on magnetic resonance imaging in children with Leigh and Leigh-like syndrome

OBJECTIVE Bilateral hypertrophic olivary degeneration on brain MRI has been reported in a few metabolic, genetic and neurodegenerative disorders, including mitochondrial disorders. In this report, we sought to analyse whether bilateral symmetrical inferior olivary nucleus hypertrophy is specifically associated with mitochondrial disorders in children. METHODS This retrospective study included 125 children (mean age, 7.6 ± 5 years; male:female, 2.6:1) diagnosed with various metabolic and genetic disorders during 2005-2012. The routine MRI sequences (T1 weighted, T2 weighted and fluid-attenuated inversion-recovery sequences) were analysed for the presence of bilateral symmetrical olivary hypertrophy and central tegmental tract or dentate nuclei signal changes. The other imaging findings and the final diagnoses were noted. RESULTS The cohort included patients with Leigh and Leigh-like syndrome (n = 25), other mitochondrial diseases (n = 25), Wilson disease (n = 40), Type 1 glutaric aciduria (n = 14), maple syrup urine disease (n = 13), giant axonal neuropathy (n = 5) and L-2 hydroxy glutaric aciduria (n = 3). Bilateral inferior olivary nucleus hypertrophy was noted in 10 patients, all of whom belonged to the Leigh and Leigh-like syndrome group. CONCLUSION Bilateral hypertrophic olivary degeneration on MRI is relatively often, but not routinely, seen in children with Leigh and Leigh-like syndrome. Early detection of this finding by radiologists and physicians may facilitate targeted metabolic testing in these children. ADVANCES IN KNOWLEDGE This article highlights the occurrence of bilateral hypertrophic olivary nucleus degeneration on MRI in children with Leigh and Leigh-like syndrome, compared with other metabolic disorders.

Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations

BACKGROUND Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. METHODS The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. RESULTS Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. CONCLUSIONS Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients.

Electro-clinical features and magnetic resonance imaging correlates in Menkes disease

BACKGROUND Epilepsy is an early and important feature in Menkes disease (MD), an X-linked recessive neurodegenerative disorder of childhood with defect in copper metabolism. There are only few reports on the electro-clinical and magnetic resonance imaging correlates in Menkes disease. The current study describes the electro-clinical features in MD in relation with the structural findings on MRI. PATIENTS AND METHODS Six patients from five families were evaluated between 2005 and 2011. Their diagnosis was based on the characteristic morphological features, microscopic evidence of pili torti and low copper and ceruloplasmin levels. All the patients underwent MRI and EEG as part of the evaluation. RESULTS All patients had classical form of MD with typical morphological features. All but one patient had refractory seizures. Seizure types included multifocal clonic seizures (n=3), myoclonic jerks (n=4) and tonic spasms (n=1). EEG was markedly abnormal in all except in the patient without clinical seizures. While focal epileptiform discharges predominated before six months of age modified hypsarrhythmia was characteristically noted thereafter. MR Imaging revealed abnormalities in all patients, with cerebral atrophy and delayed myelination being the most common observations. Other features noted were subdural effusion (n=3), leukoencephalopathy (n=3) and basal ganglia signal changes (n=1). Follow up imaging in three patients showed resolution of white matter signal intensity changes. CONCLUSIONS Electro-clinical features in Menkes disease are age dependent and evolve sequentially. White matter changes coincided with acute exacerbation of seizures. There was fair correlation between the electro-clinical features and structural findings on MRI.

Effect of valproate on the sleep microstructure of juvenile myoclonic epilepsy patients - a cross-sectional CAP based study.

OBJECTIVE Studies looking at the effect of anti-epileptic medications on sleep microstructure of patients with epilepsy are almost non-existent. The aim of this study was to compare sleep microstructural characteristics of drug-naïve juvenile myoclonic epilepsy (JME) patients with those on valproate (VPA) monotherapy. METHODS Three age- (p = 0.287) and gender- (p = 0.766) matched groups (N = 20 in each group): (1) drug-naïve JME (mean age: 21.2 ± 4.06 years; M : F = 9:11); (2) JME on VPA (mean age: 21.85 ± 4.28 years; M : F = 11:9); (3) healthy controls (mean age: 23.2 ± 3.82 years; M : F = 9:11) underwent overnight polysomnography. Scoring and analysis of arousals American Sleep Disorders Association (ASDA, 2002), cyclic alternating pattern (CAP) (Terzano et al., 2002) parameters were performed. Comparison of arousal and CAP parameters was performed using one-way ANOVA, followed by pairwise comparisons using Fishers LSD test (p ≤ 0.05). RESULTS Rapid eye movement (REM) arousal indices were higher in JME patients (Group 1 [p = 0.002] and Group 2 [p <0.001]), whereas the overall and NREM arousal indices were comparable between the three groups. CAP rate was higher in JME patients as compared to controls (p <0.001). Duration of phase A and its subtypes (p <0.001) was reduced in drug-naïve patients as compared to VPA group and controls. Finally, percentage of phase A1 (p = 0.003) was decreased and A3 (p = 0.045) was increased in drug-naïve patients as compared to VPA group and controls. CONCLUSIONS We found significant alterations in REM arousal indices and several CAP parameters in JME patients. However, many of these alterations were not seen in the valproate group. This might indicate that anti-epileptic medications such as valproate may beneficially modulate arousal instability in JME patients, and hence promote sleep quality and continuity.

Study of sleep microstructure in patients of migraine without aura

PurposeAlthough the relationship between sleep and migraine has been widely reported, studies on sleep microstructure are few. The aim was to study and compare microstructural polysomnographic characteristics in patients of “migraine without aura” (MOA) with controls.MethodsTwenty-five patients of MOA and 25 age- and gender-matched healthy controls were subjected to overnight polysomnography. Microstructural sleep analysis, including arousal and cyclic alternating pattern (CAP) analysis was performed. Arousals and CAP parameters were compared between the two groups using the Mann-Whitney U test (p ≤ 0.05).ResultsThe overall arousal index (p = 0.528) and that during non-rapid eye movement (NREM) sleep (p = 0.503) were comparable between the two groups. However, the arousal index was lower in migraineurs during rapid eye movement (REM) sleep (p = 0.001). The overall CAP rate (p = 0.020) as well as the number of CAP cycles and sequences (p = 0.032) was lower among migraineurs. The total phase A duration (p < 0.0001) was increased, and conversely, phase B duration (p = 0.001) was decreased in migraineurs. The phase A1 duration (p = 0.036) was higher in migraineurs. Finally, phase A1 (p = 0.357) index was comparable, and conversely, A2 (p < 0.0001) and A3 (p = 0.020) indices were decreased in migraineurs.ConclusionsThis study showed a decreased REM arousability as well as a decreased overall CAP rate and CAP cycling in patients with migraine as compared to controls. This indicates that there is probably an alteration of the arousal mechanisms in patients with migraine that may facilitate the occurrence of headache paroxysms during sleep.

Clinical Features, Therapeutic Response, and Follow-Up in Pediatric Anti-N-Methyl-d-Aspartate Receptor Encephalitis: Experience from a Tertiary Care University Hospital in India

AIM To describe the clinical features in pediatric anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis with specific reference to the spectrum of involuntary movements, and therapeutic response to pulsed intravenous methyl prednisolone. METHOD A total of 13 children with anti-NMDAR antibody positivity were evaluated. RESULTS Abnormal behavior, global regression, and seizures were universal. Movement disorder was characterized by hyperkinetic large amplitude, complex, multidirectional movements involving the limbs and orofacial musculature. Electroencephalogram was abnormal in all during the acute phase. All received intravenous methyl prednisolone. Plasmapheresis (n = 6) and intravenous immunoglobulin (n = 2) were administered due to subtherapeutic response during the acute illness. Monthly pulsed methyl prednisolone was administered to maintain remission. All improved substantially from the acute illness which was reflected in the modified Rankin score. Ten patients were followed up for a median duration of 10.30 ± 6.7 months. Residual symptoms included hypersomnolence, hyperphagia, hyperactivity, overfamiliarity, among others. Three had recurrence of partial syndrome that was related to delay in pulsed methyl prednisolone therapy. They improved and maintained improvement with reinitiation of pulsed methyl prednisolone therapy. CONCLUSION Anti-NMDAR encephalitis requires prolonged immunomodulatory therapy. Intravenous pulsed methyl prednisolone therapy is beneficial in inducing and maintaining remission. It is safe, effective, and well tolerated by children with anti-NMDAR encephalitis. The duration of treatment required for sustained remission and cure needs to be determined in long-term studies.

Efficacy and limitations of pulse cyclophosphamide therapy in polymyositis and dermatomyositis.

Objectives: To assess the therapeutic response of intravenous (IV) pulse cyclophosphamide therapy in polymyositis and dermatomyositis. Methods: Data of 9 patients (M:F = 2:7) who received IV pulse cyclophosphamide therapy were retrospectively analyzed. Results: The mean symptom duration was 11.33 ± 10.6 months (range, 2–34 months). The cohort comprised (1) primary idiopathic polymyositis (n = 1), (2) primary idiopathic dermatomyositis (n = 1), (3) childhood type associated with vasculitis (n = 1), and (4) associated with collagen vascular disease (n = 6). All patients improved and became clinically asymptomatic after a mean period of 12.33 ± 6.5 months (range, 4–24 months); 5 remained asymptomatic at the end of a median follow-up period of 22 months. All patients received concomitant steroid therapy, and in 6, steroids could be tapered after the initiation of IV pulse cyclophosphamide therapy. Conclusions: In this cohort of polymyositis/dermatomyositis, treatment with IV pulse cyclophosphamide was associated with improvement; the therapeutic response was sustained in majority of the patients.