Bing Neel syndrome presenting as isolated cranial nerve palsies - a case report.

Background and aims: Waldenstroms macroglobulinemia (WM) is a low-grade B cell neoplasm. Bing Neel syndrome is a rare manifestation of WM characterized by infiltrative involvement of the central nervous system. Case report: 64-year-old man, presented with 4 years history of slowly progressive diplopia and ptosis of eyes. Examination showed left oculomotor (internal and external ophthalmoplegia), with trochlear, abducens, and right partial oculomotor and abducens nerve involvement. Evaluation showed anemia of hemoglobin 10.7 g/dL, raised erythrocyte sedimentation rate of 120 mm/h and plasma albumin:globulin reversal. Serum protein electrophoresis showed a paraprotein peak in the early gamma region with elevated IgM level (3810 mg/dL) and elevated free kappa light chain level (70.1 mg/L). Bone marrow aspiration from posterior iliac crest revealed mature small lymphocytes with positive immunohistochemical markers of CD5, CD10 negativity and MYD88 mutation positivity suggestive of WM. Patient was treated with bendamustine and rituximab regimen, with no neurological improvement at the end of one year. Conclusion: This case expands spectrum of paraproteinemic neuropathy to include cranial nerve palsy. Thus, plasma cell dyscrasias have to be considered in patients with isolated ophthalmoparesis especially in elderly patients, even with other comorbidities such as diabetes mellitus.

Identification of a Novel Intronic Mutation in VMA21 Associated with a Classical Form of X-Linked Myopathy with Autophagy.

Introduction VMA21 -related myopathy is one of the rare forms of slowly progressive myopathy observed in males. Till now, there have been only a handful of reports, mainly from Europe and America, and two reports from India. Method Here, we describe a case of genetically confirmed VMA21 -associated myopathy with clinical, histopathological, and imaging features with a list of known VMA21 mutations. Results A 29-year-old man had the onset of symptoms at 18 years of age with features of proximal lower limb weakness. Muscle magnetic resonance imaging showed the preferential involvement of vasti and adductor magnus. A biopsy of the left quadriceps femoris showed features of autophagic vacuolar myopathy with vacuoles containing granular eosinophilic materials. In targeted next-generation sequencing, hemizygous mutation in the 3' splice site of intron 2 of the VMA21 gene (c.164-7 T > A) was identified and confirmed the diagnosis of X-linked myopathy with excessive autophagy. Conclusion This report expands the phenotypic and genotypic profile of VMA21 -related myopathy, with a yet unreported mutation in India.

Spinal melanoma with optic neuropathy -rare manifestation of Neurocutaneous melanosis and PET-MRI findings.

Neurocutaneous melanocytosis (NCM) is a rare, sporadic neuroectodermal dysplasia characterized by the presence of large or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. Hitherto, unreported we describe a case of NCM with optic neuropathy and spinal cord melanoma from India. A 20 year-old-lady had headache and vomiting for 3 months followed by consecutive profound painless visual impairment. Visual acuity was counting of fingers at 1 m distance in both eyes with normal fundus. There were no symptoms of spinal cord involvement. Clinical examination showed multiple small to large melanocytic nevi over the face and body. Muscle power was normal. Tendon reflexes were exaggerated. Visual evoked potential showed bilateral prolonged P100 latency (Right eye - 144 msec; Left eye - 151 msec). Brain MRI revealed leptomeningeal enhancement of brainstem, cerebellum, oculomotor and facial-abducent nerve complex without optic nerve involvement. MRI spine showed extensive dorsal thoracic cord epidural lesion extending along the entire thoracic cord segment with dorsal cord compression. Positron Emission Tomography (PET) imaging showed Fludeoxyglucose F18 (FDG) avidity along D1-D12 levels of spinal cord. Biopsy from the cord lesion was suggestive of meningeal melanoma. Here we document a rare case of late onset NCM with intracranial meningeal infiltration and asymptomatic large epidural lesion of spinal cord, expanding its phenotypic spectrum. Optic neuropathy in NCM has not been reported earlier. Periodic screening of brain and spine is recommended for early prognostication and lesion identification in NCM.

Neuroradiological findings in GAA-FGF14 ataxia (SCA27B): more than cerebellar atrophy.

Background: GAA-FGF14 ataxia (SCA27B) is a recently reported late-onset ataxia caused by a GAA repeat expansion in intron 1 of the FGF14 gene. Initial studies revealed cerebellar atrophy in 74-97% of patients. A more detailed brain imaging characterization of GAA-FGF14 ataxia is now needed to provide supportive diagnostic features and earlier disease recognition. Methods: We performed a retrospective review of the brain MRIs of 35 patients (median age at MRI 63 years; range 28-88 years) from Quebec (n=27), Nancy (n=3), Perth (n=3) and Bengaluru (n=2) to assess the presence of atrophy in vermis, cerebellar hemispheres, brainstem, cerebral hemispheres, and corpus callosum, as well as white matter involvement. Following the identification of the superior cerebellar peduncles (SCPs) involvement, we verified its presence in 54 GAA-FGF14 ataxia patients from four independent cohorts (Tübingen n=29; Donostia n=12; Innsbruck n=7; Cantabria n=6). To assess lobular atrophy, we performed quantitative cerebellar segmentation in 5 affected subjects with available 3D T1-weighted images and matched controls. Results: Cerebellar atrophy was documented in 33 subjects (94.3%). We observed SCP involvement in 22 subjects (62.8%) and confirmed this finding in 30/54 (55.6%) subjects from the validation cohorts. Cerebellar segmentation showed reduced mean volumes of lobules X and IV in the 5 affected individuals. Conclusions: Cerebellar atrophy is a key feature of GAA-FGF14 ataxia. The frequent SCP involvement observed in different cohorts may facilitate the diagnosis. The predominant involvement of lobule X correlates with the frequently observed downbeat nystagmus.

Hippocampal volume and recovery profile following propofol sedation in children undergoing magnetic resonance imaging: An exploratory study.

Background: Reduction in the hippocampal volume may contribute to agitated and delayed emergence after anesthesia in epilepsy surgery. We hypothesized that hippocampal volume and the duration of various recovery parameters after a short duration of sedation may be correlated. The primary objective was to evaluate the correlation between hippocampal volumes with time to recovery after the stoppage of propofol infusion. Methods: After obtaining Institute Ethical Clearance, we included all children of the age group 5-17 years, who needed sedation for brain magnetic resonance imaging (MRI) for at least 20-60 minutes for the evaluation of epilepsy. The hippocampal volume was estimated bilaterally in the pre-contrast volumetric magnetization-prepared rapid gradient-echo (MPRAGE) brain imaging by the radiologist using statistical parametric mapping. The correlation of hippocampal volume with recovery and time to discharge (assessed by the modified Aldrete score (MAS)) was obtained using Spearman's correlation coefficient (rho). A rho > ± 0.5 was considered a good correlation between the variables. Results: Data on a total of 18 children (10 males and 8 females) who required sedation for an MRI were studied over a period of six months. The correlation coefficients of right and left corrected hippocampal volumes with time to spontaneous eye opening were -0.052 and -0.195, respectively. The correlation coefficients of right and left corrected hippocampal volumes with time to respond to oral commands were -0.017 and -0.219, respectively. Conclusion: There was a weak negative correlation between hippocampal volumes and recovery parameters after a short duration of sedation with propofol in children.

Intracranial lipoma: an incidental finding and a rare cause of secondary headache.

AIM OF THE STUDY: Expand the differential diagnosis of secondary headache to include rare intracranial tumours, detected incidentally on brain imaging. Intracranial lipomas are rare congenital malformations, and are usually pericallosal asymptomatic midline lesions. However, some cases present with headache and seizures. Symptomatic intracranial lipomas are very rare and often detected incidentally on brain imaging. METHODS: We present a 52-year-old woman referred to our tertiary centre with a history of hypothyroidism presented with headache for 2 years. She had generalised body pains for six months. Her headache was persistent despite being on medications. Physical and neurological examination was unremarkable. Her visual acuity and fundus examination were normal. RESULTS: Her brain imaging revealed a lesion over the corpus callosum and in the interhemispheric fissure with signal attenuation on the fat suppression sequence, features suggestive of curvilinear pericallosal lipoma. Symptomatic treatment with analgesics and anti-inflammatory agents were slightly effective. It is debatable whether tumour removal is required, as the risks of surgical intervention far outweigh the potential benefits. CONCLUSION: Corpus callosal lipoma is a rare and unrecognised cause of secondary headache. It should be suspected in patients with an atypical headache without papilledema and who are unresponsive to analgesics. This may be the only presenting feature of intracranial lipomas rendering it even more difficult to suspect and diagnose, thus emphasising the importance of evaluating secondary headaches. Diagnosis is important because long-term follow-up may be required if patients develop new focal deficits, which may necessitate surgical intervention.

Transcranial ultrasonographic evaluation of effect of ventriculoperitoneal shunt on intracranial dynamics: A prospective observational study.

BACKGROUND: Transcranial sonographic (TCS) evaluation of optic nerve sheath diameter (ONSD), third ventricular diameter (TVD) and mean flow velocities (Vm) and pulsatility index (PI) of middle cerebral artery (MCA) can provide important insights to the change in intracranial dynamics following ventriculo-peritoneal (VP) shunt surgery. The primary objective of this study was to observe changes in ONSD values following VP shunt at 12 h, compared to pre-VP shunt values. METHODS: After obtaining ethical approval, patients admitted with a diagnosis of hydrocephalus posted for a VP shunt surgery were prospectively enrolled. TCS evaluation was done before induction of anesthesia and 12-hour post-VP shunt surgery. We recorded the values of ONSD, TVD and Vm and PI MCA at both time points. RESULTS: Thirty-four patients (19 male) were evaluated for ONSD and for the improvement of symptoms. Transtemporal window could not be obtained in six patients. At 12 h following VP shunt, bilateral median ONSD values reduced significantly from their pre-VP shunt values [right ONSD- 0.62 (0.59-0.64) to 0.53 (0.5-0.54) mm (p < 0.001); left ONSD- 0.62 (0.59-0.63) to 0.53 (0.5-0.54) mm (p < 0.001)]. Similarly, the median TVD at 12 h post-VP shunt reduced significantly from its pre-VP shunt measurements [0.97 (0.85-1.09) to 0.74 (0.7-0.84) cm]. PI MCA values reduced significantly, while Vm MCA values increased significantly from the pre-VP shunt values. CONCLUSION: VP shunt reduced the ONSD, TVD, PI MCA and increased the Vm MCA after shunt surgery as early as 12hrs.

Unmasking bipolarity in recurrent depressive disorder following herpes simplex virus triggered n-methyl-D-aspartate encephalitis.

OBJECTIVE: Herpes simplex virus (HSV) infection triggered n-methyl-D-aspartate (NMDA) encephalitis can lead to varied neuropsychiatric manifestations, including movement disorders and manic symptoms. HSV is known to affect the same brain regions as in secondary mania. METHOD: We present a 35-year-old female diagnosed with recurrent depressive disorder (RDD) who developed NMDA encephalitis triggered by HSV infection. RESULT: HSV-triggered NMDA encephalitis led to a manic switch in a woman with RDD on antidepressants, along with the new onset of dyskinetic movements. CONCLUSION: A neurological insult predisposed our patient to the variable effects of antidepressant drugs.

Cough elixir overdose causing toxic leuco-encephalopathy and serotonin syndrome.

Acute toxic leukoencephalopathy and serotonin syndrome are rare neurological complications associated with various drugs and toxins, some of which overlap. However, the co-occurrence of these conditions is poorly documented. We present the case of a 14-year-old boy who suddenly developed altered consciousness and autonomic dysfunction after consuming excessive quantities of cough remedies containing dextromethorphan, chlorphenamine, dichlorobenzyl alcohol, and amylmetacreson. Magnetic resonance imaging of the brain revealed distinct white matter lesions. With supportive care, the patient rapidly improved, and the magnetic resonance imaging abnormalities disappeared. The swift resolution, typical magnetic resonance imaging findings, and a history of exposure to drugs affecting the central nervous system's serotonergic system suggested concurrent acute toxic leukoencephalopathy and serotonin syndrome. The components of cough medications can be hazardous in overdose due to their potential to enhance serotonin toxicity and cause direct or indirect central nervous system white matter damage. Early recognition and appropriate treatment are essential for recovery.

Monomelic Amyotrophy/Hirayama Disease: Surgical Outcome in a Large Cohort of Indian Patients.

BACKGROUND: Hirayama disease (HD) is a cervical compressive myelopathy. Anterior cervical discectomy and fusion (ACDF) is identified as the best surgical approach. We evaluated surgical outcomes and factors influencing ACDF in HD. METHODS: Between 2015 and 2019, 126 patients with HD underwent ACDF. Contrast magnetic resonance imaging of the cervical spine in full flexion was performed. Clinical examination and preoperative/postoperative assessment of hand function using Fugl-Meyer assessment, Jebsen-Taylor hand function test, and handheld dynamometry were performed at 3-monthly intervals for 1 year. Surgical outcomes were assessed as per the Odom criteria and Hirayama outcome questionnaire. RESULTS: Age at onset and duration of illness were 12-31 years (mean, 18 ± 2.7) and 1-96 months (32.7 ± 24.4), respectively. All patients had progressive weakness and wasting of the affected limb. Cord atrophy was seen in 97.1%, with epidural detachment and engorgement of the posterior epidural venous plexus in all. All patients underwent ACDF. Of these patients, 54% had an excellent/good outcome and 39% had a satisfactory outcome as per the Odom scale at last follow-up (mean, 44.9 ± 16.5 months) after surgery. Handheld dynamometry showed improvement from preoperative values to 1 year follow-up. Duration of illness and age at onset had a negative correlation and the preoperative Fugl-Meyer score had a positive correlation with improvement. CONCLUSIONS: ACDF resulted in remarkable improvement or stabilization in neurologic deficits in many patients with HD. Because motor disability ensues over time, early surgical intervention during the progressive phase is advocated.

A Novel Mutation in Frabin (FGD4) Causing a Mild Phenotype of CMT4H in an Indian Patient.

Charcot-Marie-Tooth disease 4H(CMT4H) is an autosomal recessive demyelinating form of CMT caused by FGD4/FRABIN mutations. CMT4H is characterized by early onset and slowly progressing motor and sensory deficits in the distal extremities, along with foot deformities. We describe a patient with CMT4H who presented with rapidly progressing flaccid quadriparesis during the postpartum period, which improved significantly with steroid therapy. Magnetic resonance imaging and ultrasonography demonstrated considerable nerve thickening with increased cross-sectional area in the peripheral nerves. A nerve biopsy revealed significant demyelination and myelin outfolding. This is the first report of an Indian patient with a novel homozygous nonsense c.1672C>T (p.Arg558Ter) mutation in the FGD4 gene, expanding the mutational and phenotypic spectrum of this disease.

Pneumothorax in Acute Neurologically Ill COVID-19 Positive Patients: A Brief Report.

Background: Pneumothorax is reported as a complication of coronavirus disease-2019 (COVID-19). The present report describes the incidence, clinical characteristics, and outcomes of pneumothorax in acute neurologically ill COVID-19 positive patients admitted to the COVID-19 neuro-intensive care unit (CNICU). Methods: In this retrospective study, pneumothorax was identified by reviewing chest radiographs of acute neurologically ill patients with and without associated COVID-19 admitted to the CNICU and non-COVID-19 NICU, respectively, from July to November 2020. The clinico-epidemiological characteristics of acute neurologically ill COVID-19 positive patients with pneumothorax are described. Results: The incidence of pneumothorax was 17% (8/47) in acute neurologically ill COVID-19 positive patients in the CNICU and 14.6% (6/41) in patients who received mechanical ventilation (MV). In contrast, the incidence of pneumothorax in acute neurologically ill non-COVID-19 patients admitted to the NICU was 3.7% (7/188) and 0.69% (1/143) in patients receiving MV. Conclusion: In our study, the incidence of pneumothorax was higher in patients with concomitant neurological and COVID-19 diseases than in acute neurologically ill non-COVID-19 patients managed during the same period in the ICUs.

Role of magnetoencephalography in predicting the epileptogenic zone and post-operative seizure outcome - A retrospective study.

PURPOSE: Study assessed the role of MSI in predicting the post-operative seizure outcome. METHODS: This retrospective study included patients who underwent MEG and epilepsy surgery and had a minimum 6 months of postoperative follow-up. Concordance of MEG cluster with post-surgical resection cavity was classified as follows Class I) Concordant and region-specific, Class II) Concordant and region non-specific, Class III) Concordant lateralization only and Class IV) Discordant lateralization. The relationship between MSI concordance and post-operative seizure outcome was assessed. RESULTS: A total of 183 patients (M: F = 109:74) were included. The mean age at onset of seizures: 8.0 ± 6.4 years. The dipoles were frequent in 123(67.2 %). The primary cluster orientation was regular in 59 (32.2 %) and mixed in 124 (67.8 %) patients. Concordance between MEG and resection cavity: Class I - 124 (67.8 %), class II- 30 (16.4 %), class III- 23 (12.6 %), and class IV- 6 (3.3 %). The post-surgically mean duration of follow-up was 19.52 ± 11.27 months. At 6-month follow-up period, 144 (78.7 %) patients had complete seizure freedom out of which 106 (73.6 %) had class I concordance. Concordance of MEG with resection cavity was associated with a good outcome at 6 months (p = 0.001), 1 year (p = 0.001), 2 years (p = 0.0005) and 5 years (p = 0.04). MEG cluster characteristics had no association with seizure outcome except the strength of the cluster and outcome at 3 years (p = 0.02) follow-up. CONCLUSION: The study supports that the complete resection of the MEG cluster had high chance of seizure-freedom and can be used as a complementary noninvasive presurgical evaluation tool.

An Illustrative Review of the Pathomechanisms of Symptomatic Developmental Venous Anomalies.

OBJECTIVE: Symptomatic developmental venous anomalies (DVAs) are rare. Here, we illustrate the varied clinicoradiologic profiles of symptomatic DVAs and contemplate the mechanisms that render these (allegedly) benign entities symptomatic supported by a review of literature. METHODS: Institutional databases were searched to identify cases of symptomatic DVAs. Clinical and imaging (angiographic and cross-sectional) data of 9 cases with 11 neurovascular symptoms consequent to inflow/outflow perturbations and mechanical obstruction that manifested because of the strategic topography of underlying DVAs were analyzed. A review of the existing literature on DVAs in agreement with our case series was performed on publications retrieved from the PubMed database. RESULTS: Symptoms secondary to venous hypertension arising from flow-related perturbations were broadly divided into those arising from restricted outflow and increased inflow. Restricted outflow occurred because of collector vein stenosis (n = 2) and collector vein/DVA thrombosis (n = 3), whereas the latter pathomechanism was initiated by arterialized/transitional DVAs (n = 2). A mechanical/obstructive pathomechanism culminating in moderate supratentorial ventriculomegaly was noted in 1 case. One patient was given a diagnosis of hemorrhage associated with a cavernoma. CONCLUSIONS: Awareness and contextualization of potential flow-related perturbations and mechanical insults that render DVAs symptomatic aid in accurate diagnosis, management, and prognostication.

Mastoid fluid signal in acute cerebral venous thrombosis is is associated with increased clot burden.

PURPOSE: Mastoid air cell abnormalities in the form of hyperintense T2 fluid signal have been reported in cases of acute Cerebral Venous Thrombosis (CVT) without otologic infection and have been hypothesized to be a result of venous congestion rather than infectious mastoiditis. The aim of this study was to investigate a link between the spectrum of mastoid abnormalities and clot burden in patients with acute CVT. METHODS: A retrospective study of adult patients admitted to the National Institute of Mental Health and Neurosciences between 2016 and 2023 who were diagnosed with acute CVT and had no clinical evidence of active or recent ear infections was conducted. Pre- and post-contrast MR Images were analyzed to identify the dural sinuses and/or cerebral veins involved and the presence of fluid signal in the mastoid. Fluid signal in the mastoid was graded from 0 to 3 as described by Shah et al- no fluid signal (grade 0), thin curvilinear hyperintensities (grade 1), thick crescenteric hyperintensities (grade 2), and complete hyperintensity (grade 3). Clot Burden Score (CBS) was calculated by assigning one point for each sinus involved, one point for extension of thrombus into the intracranial Internal Jugular Vein (IJV), one point for thrombosis of cortical veins and one point for thrombosis of deep cerebral veins. RESULTS: A total of 89 patients with acute CVT were included in the final analysis. Median time from presentation to MRI was 2 days (range 0-13). 51 patients (57.3%) had fluid signal in the mastoid air cells on T2-weighted images, of whom 33 showed mucosal contrast enhancement. Higher grade of fluid signal in the mastoid was present ipsilateral to the side of venous thrombosis in 59 out of 60 patients with posterior fossa CVT. CBS was significantly different between patients with different grades of fluid signal (p = 0.002). Grade 2-3 fluid signal was associated with higher clot burden (CBS > 3) in both the entire study population (n = 89) - OR = 8.281, 95 %CI: 2.758-24.866 (p < 0.001) and among patients with posterior fossa CVT - OR = 4.375, 95 %CI: 1.320-14.504 (p = 0.016). Among patients with posterior fossa CVT, grade 2-3 fluid signal was associated with left sided transverse and/or sigmoid sinus thrombosis - OR = 5.600, 95 %CI: 1.413-22.188 (p = 0.014), and extension of thrombosis into the IJV - OR = 4.606, 95 %CI: 1.162-18.262 (p = 0.030). CONCLUSION: T2 fluid signal in the mastoid is associated with venous congestion in adults with acute CVT without evidence of otologic infection. Moderate-to-severe T2 fluid signal in the mastoid air cells is associated with increased clot burden.

Utility of 3D T1-weighted turbo spin echo black blood sequence for the diagnosis of cerebral venous thrombosis.

PURPOSE: Accurate assessment of dural sinus, deep and cortical venous thrombosis on MR imaging is challenging. The aim of this study is to evaluate the accuracy of 3D-T1 turbo spin echo (T1S), sequences in detecting venous thrombosis and comparing it with susceptibility-weighted imaging (SWI), magnetic resonance venography (MRV) and post contrast T1 magnetization-prepared rapid acquisition gradient echo (T1C). METHODS: A blinded retrospective observational analysis of 71 consecutive patients evaluated for cerebral venous thrombosis (CVT) and 30 control patients was performed. Multimodality reference standard adopted included T1C, SWI with MRV. Sub-analyses in superficial, deep and cortical venous segments were performed in addition to correlation of signal intensity of thrombus with the clinical stage. RESULTS: A total of 2222 segments in 101 complete MRI examinations were evaluated. Sensitivity/specificity/positive predictive value/negative predictive value/accuracy and precision of T1S for detection of cortical vein thrombosis was 0.994/1/1/0.967/0.995/1, 1/0.874/0.949/1/0.963/0.950 for detection of superficial venous sinus thrombosis and 1/1/1/1/1/1 for deep venous thrombosis. The AUC yield for T1S was 0.997 for cortical, 1 for deep and 0.988 for superficial venous segments. CONCLUSION: T1S paralleled the accuracy of conventional sequences in the overall detection of CVT but showed superior accuracy in the detection of cortical venous thrombosis. It makes a fitting addition to the CVT MRI protocol in scenarios demanding negation of gadolinium administration.