Aceruloplasminemia with Novel Mutation, with IgG4 Related Pachymeningitis - Occam's Razor or Hickam's Dictum?

To report a patient with concomitant aceruloplasminemia (with a novel mutation) and IgG4-related pachymeningitis and to hypothesize on the possible relation between the two diseases. Clinical, radiological, and laboratory features of a 56-year-old lady with chronic headache, bifacial palsy, and cerebellar signs are described. Pathophysiology of aceruloplasminemia leading to hyperferritinemia and consequent immune activation is elucidated. A coherent explanation of IgG4-related pachymeningitis resulting from aceruloplasminemia and hyperferritinemia is given. The patient has aceruloplasminemia with a novel nonsense mutation. She also suffers from biopsy-proven IgG4 related pachymeningitis as per standard criteria. These two seemingly unrelated illnesses are linked by hyperferritinemia. This case is a fine example of Occam's razor. Immune dysfunction and autoimmune disorders in aceruloplasminemia need to be explored through further studies to look for causal associations.

Impact of Thymectomy on Crisis Incidence and Quality of Life amongst Generalised Myasthenia Gravis Patients.

Background: Thymectomy, combined with corticosteroids, immunosuppressive agents, and cholinesterase inhibitors, has been accepted as the standard treatment for myasthenia gravis (MG) patients. Data on the effect of thymectomy on occurrence of myasthenic crisis are few. Objectives: To assess the long-term impact of thymectomy in patients with generalized Myasthenia gravis (GMG) in terms of occurrence of myasthenia crisis and quality of life. Methods: A retrospective analysis of 274 clinical records of patients diagnosed with myasthenia gravis (MG) in Nizam's institute of medical sciences (NIMS), a tertiary level teaching hospital between January 2000 and December 2015 was done. Severity of the disease was assessed using Myasthenia Gravis Foundation of America (MGFA) classification and quantitative myasthenia gravis (QMG) score. Myasthenia crisis was diagnosed in our patients when they required ventilator assistance due to respiratory failure caused by muscle weakness (MGFA class V). Quality of life (QoL) was assessed. Results: Of 230 cases included in the final analysis, 108 (46.9%) underwent thymectomy. Posttreatment crisis occurred in 53.3% of the nonthymectomy subjects, and 25.9% of thymectomy group (P < 0.001). In multivariate logistic regression analysis, after controlling for the effect of gender, age at diagnosis and grade of the disease, the odds ratio of myasthenic crisis in people with thymectomy was 0.186.(95% CI 0.087 to 0.387, P = 0.001). No statistically significant differences were observed in quality of life scores between thymectomy and nonthymectomy groups, either before (P = 0.86) or after surgery (P = 0.939). Conclusions: The odds of myasthenia crisis was lesser in people, who underwent thymectomy even after controlling for MGFA grade and other potential confounders but no significant differences in quality of life were found with thymectomy.

Impact of the COVID-19 Pandemic on the Frequency, Clinical Spectrum and Outcomes of Pediatric Guillain-Barré Syndrome in India: A Multicentric Ambispective Cohort Study.

Objective: To study impact of COVID-19 pandemic on frequency, clinical/electrophysiological profile and treatment outcomes in pediatric Guillain-Barré syndrome (GBS). Background: GBS is the most frequent cause of pediatric acute flaccid paralysis. The effect of the COVID-19 pandemic on pediatric GBS is unclear in the literature. Methods: We conducted an ambispective, multicentric, cohort study involving 12 of 27 centres in GBS Consortium, during two periods: pre-COVID-19 (March-August 2019) and during COVID-19 (March-August 2020). Children ≤12 years who satisfied National Institute of Neurological Diseases and Stroke criteria for GBS/variants were enrolled. Details pertaining to clinical/laboratory parameters, treatment and outcomes (modified Rankin Scale (mRS) at discharge, GBS Disability score at discharge and 3 months) were analysed. Results: We enrolled 33 children in 2019 and 10 in 2020. Children in 2020 were older (median 10.4 [interquartile range 6.75-11.25] years versus 5 (2.5-8.4) years; P = 0.022) and had more sensory symptoms (50% versus 18.2%; P = 0.043). The 2020 group had relatively favourable mRS at discharge (median 1 (1-3.5) versus 3 (2-4); P = 0.042) and GBS disability score at 3 months (median 0 (0-0.75) versus 2 (0-3); P = 0.009) compared to 2019. Multivariate analysis revealed bowel involvement (P = 0.000) and ventilatory support (P = 0.001) as independent predictors of disability. No child in 2020 had preceding/concurrent SARS-CoV2 infection. Conclusions: The COVID-19 pandemic led to a marked decline in pediatric GBS presenting to hospitals. Antecedent illnesses, clinical and electrophysiological profile of GBS remained largely unchanged from the pre-pandemic era.

Clinicoradiological Profile of Superficial Middle Cerebral Vein Thrombosis.

BACKGROUND: The diagnosis of isolated cortical vein thrombosis (ICVT) involving superficial middle cerebral vein (SMCV) remains challenging even in the present era of modern MRI protocols. OBJECTIVE: The purpose of this study is to review the clinical and radiological characteristics of SMCV thrombosis in our hospital. METHODS: Chart review of cases of SMCV thrombosis admitted in a tertiary care university hospital in South India during a 1-year period from September 2015 to August 2016. RESULTS: Five SMCV thrombosis patients were identified and presented with focal seizures. Neuroimaging showed edema (with or without hemorrhage) of cortex and white matter of inferior frontal gyrus, temporal pole, superior temporal gyrus, insular cortex, and external capsule. The thrombosis of SMCV was demonstrated by Spin echo T1-weighted, GRE-weighted axial, and postcontrast T1-weighted images in coronal and sagittal planes, with a slice thickness of <3 mm. Four received anticoagulation and all improved rapidly and completely. CONCLUSION: SMCV thrombosis should be considered in patients having recent onset seizures in appropriate setting based on MRI evidence of parenchymal edema and/or hemorrhage in the perisylvian region along with evidence of thrombosed vein in that region. Appropriate imaging sequences help in confirmation of diagnosis.

Serum B12, Homocysteine Levels, and their Effect on Peripheral Neuropathy in Parkinson's Disease: Indian Cohort.

BACKGROUND: Cobalamin deficiency, either due to dietary inadequacy or increased consumption attributable to levodopa-mediated metabolic disturbance, and resultant hyperhomocysteinemia may contribute to peripheral neuropathy (PN) in Parkinson's disease (PD). AIM: The aim of the study is to assess the prevalence of Vitamin B12 deficiency, hyperhomocysteinemia in Indian PD patients, and their association with PN. MATERIALS AND METHODS: Clinical details were collected in 93 patients over a period of 2 years. Seventy controls were included in the study. Serum B12, homocysteine, folate, electroneurography, and autonomic function tests were done. The prevalence of B12 deficiency and hyperhomocysteinemia in PD patients and controls was assessed. The association of B12 and homocysteine levels with patients' age, disease duration, levodopa equivalent daily dose, cumulative levodopa dose, Unified Parkinson's Disease Rating Scale-III off score, modified Hoehn and Yahr score, and presence or absence of PN was studied. RESULTS: Serum B12, homocysteine levels, prevalence of B12 deficiency, and hyperhomocysteinemia were no different between cases and controls. Seven of 93 (9.68%) PD patients had PN. The median values of serum B12, folate, and homocysteine levels across patients with or without PN could not be compared as only seven of our patients had PN. CONCLUSION: The prevalence of B12 deficiency, hyperhomocysteinemia, and incidence of PN among our patients is very less when compared to the Western population. The conjecture that PN in PD patients may be secondary to B12 deficiency/hyperhomocysteinemia stands as a speculation.

Validation of the 2015 diagnostic criteria for neuromyelitis optica spectrum disorders in a cohort of South Indian patients.

BACKGROUND: Neuromyelitis Optica spectrum disorders (NMOSD) are one of the most common CNS demyelinating disorders as they will present with disabling recurrent demyelinating attacks. Hence, it is of paramount importance to diagnose early, and early diagnoses and intervention will prevent further relapses associated with NMOSD. New international consensus criteria have been proposed and studies validating its application towards diagnoses of NMOSD in south Asian population are meagre. Hence we validated the proposed International Panel for NMO Diagnosis (IPND), 2015 criteria to study the clinical, demographic profile and sero-status of patients who are presenting with core clinical symptoms of NMOSD in South India and compare it with 2006 criteria. METHODS: A retrospective study was conducted in a tertiary hospital for a period of one year. Patients who had at least one core clinical feature of NMOSD were included. Demographics and clinical data were recorded and analysed. Cases were evaluated using 2015 IPND and 2006 criteria for all patients, data was analysed using SPSS. RESULTS: A total of 110 patients were included and 91(82.72%) patients fulfilled IPND 2015 criteria. Out of 91 patients, 70 patients were AQP4 antibody positive and 21 were negative. Out of 110, only 30 (27.2%) satisfied 2006 criteria (24 or 80% were seropositive). 2015 criteria were more sensitive in identifying 61 new NMOSD cases juxtaposed to 2006 criteria, this difference was statistically significant (P<0.05). CONCLUSION: The 2015 IPND criteria were more sensitive and specific than previous 2006 criteria as it covered diverse clinical manifestations of NMOSD. Applying this criteria, NMOSD could be diagnosed among patients with monophasic illness, isolated recurrent optic neuritis, isolated recurrent myelitis, cerebral syndrome, diencephalic syndrome, brainstem syndrome and area postrema syndrome, thus improving the diagnostic yield.

Worsening Guillain-Barré syndrome: harbinger of IRIS in HIV?

We report an HIV patient aged 38 years with acute inflammatory demyelinating polyradiculoneuropathy subtype of Guillain-Barré syndrome (GBS) as the only manifestation of seroconversion and worsening of GBS being the harbinger of immune reconstitution inflammatory syndrome (IRIS). To date, only 5 cases of GBS during IRIS are reported. They manifested either during the third week or later after starting highly active antiretroviral therapy (HAART). Our patient witnessed worsening weakness by fifth day after starting HAART, even before the occurrence of Pneumocystis jirovecii pneumonia, cautioning one of the impending serious complications of IRIS and helped us initiate steroids at an early date.

Intrasinus thrombolysis in cerebral venous sinus thrombosis: Experience from a university hospital, India.

BACKGROUND: Intrasinus thrombolysis (IST) is believed to improve outcome in patients of cerebral venous sinus thrombosis (CVST) unresponsive to heparin. PURPOSE: The purpose of this article is to describe our experience with IST in patients of CVST unresponsive to heparin. MATERIALS AND METHODS: Hospital databases were searched, and patients with CVST who underwent IST from May 2011 to March 2014 were identified. Data on clinical presentation, duration of symptoms, and indications and dosage of IST were retrieved and outcomes analyzed. RESULTS: Twenty-four patients received IST. The presenting symptoms included headache (n = 19), seizures (n = 16), and altered sensorium (n = 14); signs included papilledema (n = 20) and hemiparesis (n = 15). Nineteen patients received unfractionated heparin (UFH), four received low-molecular-weight heparin (LMWH), and one received both. In one patient, microcatheter could not be passed, two patients bled intracranially, and three had nonintracranial bleeds. Among four deaths, none was due to iatrogenic bleeding. On discharge, 10 patients (43.5%) had good improvement with the modified Rankin Scale (score; mRS) ≤2 and eight (34.8%) had partial improvement with mRS = 3, 4. Seventeen patients (73.9%) had mRS ≤2 at 6 months follow-up. Bleeding complications of urokinase were less than those of alteplase. Recanalization of the involved sinuses was achieved in all. Early intervention led to successful recanalization. Functional recanalization decreased intracranial bleeding. CONCLUSION: Till date, our study is the largest series of IST in CVST reported from India. IST may be more effective than systemic heparin anticoagulation in moribund and unresponsive patients despite the potential for bleeding manifestations. Functional recanalization is adequate for good results. However, a randomized prospective study comparing heparin anticoagulation with IST is warranted.