Recurrent thunderclap headache after endovascular embolization of pial AV malformation by onyx material.

Thunderclap headache is a sudden severe headache with onset to peak within one minute. Multiple excruciating, short-lived thunderclap headaches over a few days to weeks are highly suggestive of reversible cerebral vasoconstriction syndrome (RCVS). RCVS can be primary or secondary to several factors, but it is rarely described after neuro-endovascular procedures using onyx material. A 10-year-old child presented with RCVS heralded by recurrent thunderclap headache following endovascular embolization of pial arteriovenous malformation with onyx material (contains organic solvent dimethyl sulfoxide). Dimethyl sulfoxide is an angiotoxic material that can cause dysregulation of cerebral vascular tone triggering reversible cerebral vasoconstriction syndrome. Recurrent thunderclap headache after embolization procedures using onyx material should prompt for the diagnosis of reversible cerebral vasoconstriction syndrome.

Clinical and Radiological End Points to Stop Anti-Tubercular Treatment in Central Nervous System Tuberculoma and Predictors of Poor Outcome: A Retrospective Study.

The clinical and radiological end points to stop anti-tubercular treatment in central nervous system (CNS) tuberculoma are not known. This retrospective study was done to determine end points to stop anti-tubercular treatment and find the predictors of poor outcome in patients with CNS tuberculoma. Patients who were admitted with a diagnosis of brain/spine tuberculoma between January 2015 and December 2019 and who completed a minimum of 1-year follow-up were enrolled. Clinical and radiological end points to stop anti-tubercular treatment and predictors of death and poor outcome (modified Rankin scale > 2) were analyzed. One hundred and eight patients (male-to-female ratio, 47 [43.5%]:61 [56.5%]; brain tuberculoma, 102; spinal cord tuberculoma, 14; brain and spinal cord tuberculoma, 8) were included in the study. Median duration of anti-tubercular treatment was 24 months. Radiological resolution of tuberculoma (resolution of gadolinium-enhancing lesion, gliosis, calcification, cord atrophy, or syrinx formation) and radiological halt (no increase in size/number of tuberculoma on magnetic resonance imaging scans done 6 months apart) were used as end points to stop anti-tubercular treatment in 69 and 7 patients, respectively. Seven patients stopped their treatment by themselves, and 25 patients died. Altered sensorium, motor weakness, infarcts, hydrocephalus, and constitutional symptoms of tuberculous meningitis were predictors of poor outcome or death in CNS tuberculoma patients. Radiological resolution or radiological halt of brain/spinal cord tuberculoma was a reasonable end point to stop anti-tubercular treatment. However, this may require 24 months or more of anti-tubercular treatment. Associated tuberculous meningitis and its complications portend a poor prognosis.

Posterior Reversible Encephalopathy Syndrome in a Child With Renovascular Hypertension.

A 6-year-old child presented with headache for 1 month and seizures followed by altered consciousness for 1 day. He had new-onset daily occipital headache for 1 month of mild to moderate severity and pulsating character. What is your diagnosis?

The Psychosocial Impact of COVID-19 on an Adult Indian Population.

BACKGROUND: Coronavirus disease (COVID-19) was a pandemic with many physical, psychological, and socioeconomic effects. COVID-19 caused a global increase in anxiety and depression because of its novelty, high infectivity, varied presentation, and unpredictable mortality. In the face of collapsing healthcare facilities, monetary setbacks, and loneliness because of lockdowns, people were anxious, and this was compounded by media sensationalism. We aimed to study the psychosocial impact of COVID-19 on the adult Indian population. METHODS: An online survey using SurveyMonkey was floated through WhatsApp messages in April 2020, using the 'chain-referral sampling' method. Responses from individuals >18 years were included, and questions included age, sex, occupation, demographics, and socioeconomic conditions. The prevalence of anxiety and depression was assessed using the Generalized Anxiety Disorder (GAD-7) and the Patient Health Questionnaire (PHQ-9) scales. Data was analyzed using IBM SPSS software, and predictors of anxiety and depression were assessed. RESULTS: A total of 2640 responses from individuals between 18 years and 81 years were analyzed, of which 39% were from females and 85% from those <50 years of age. There were students (15.6%), teachers (10.7%), healthcare workers (16.8%), homemakers (9%), and daily wage laborers (4.1%), among others. Nearly 80% lived in cities, 55% had salaried jobs, 37% were working from home, 22% were temporarily unemployed, 10% were feeling work stress, 11% had increased alcohol intake, and 7.5% saw an increase in domestic violence. The income of 50% was adversely affected. Nearly 50% of our respondents had some symptoms of anxiety, and 23% had significant anxiety (GAD ≥5). The presence of anxiety was significantly higher in females, younger adults, city dwellers, healthcare workers, unemployed people, individuals living away from home, those without fixed salaries, those with work stress, and in people whose incomes had been adversely affected by the pandemic. On logistic regression analysis, female sex, younger age, unemployment, lack of salaried jobs, work stress, being a healthcare worker, and media reports were independent predictors of anxiety. About 60% of our respondents had some symptoms of depression, with 26% having significant depression (PHQ-9 ≥5). The presence of depression was significantly higher in females, younger adults, city dwellers, unemployed people, individuals living away from home without fixed salaries, and people with work stress. On logistic regression analysis, younger age, female sex, unemployment, lack of salaried jobs, work stress, and media reports were independent predictors of depression. Among our respondents, 70% used the time during the lockdown to study, 77% caught up with their families, and 56% reconnected with hobbies. Nearly 88% of our respondents had adjusted to their changing circumstances, helped by their religious beliefs and faith, the support of family and friends, good government measures, and the assurance of healthcare. CONCLUSIONS:  Significant anxiety and depression were seen in 23% and 26% of respondents, respectively. Being a healthcare worker was an independent predictor of anxiety. Female sex, younger age, unemployment, work stress, and sensational media reports were independent predictors of both anxiety and depression.

Spinal cord involvement in COVID-19: A review.

Context: Recent literature points towards myelitis, like encephalitis, as a common central nervous system complication of COVID-19. This review elaborates on disorders of the spinal cord caused by the SARS-CoV-2 virus.Objectives: To review the published data about SARS-CoV-2-associated spinal cord disorders and assess their clinical, neuroimaging, treatment, and prognostic aspects.Methods: The PubMed and Google Scholar databases were searched for published cases using the search items "COVID-19 OR SARS-CoV-2 AND myelitis", "COVID-19 OR SARS-CoV-2 AND myelopathy", and "COVID-19 OR SARS-CoV-2 AND spinal cord".Results: Thirty-three isolated cases were included in the present review, of which 14 were aged 60 years and above (range: 3-70 years). Eighteen patients had lung abnormalities on chest imaging. Eight patients had developed either an areflexic paraparesis or quadriparesis. In 17 patients, neuroimaging demonstrated longitudinally extensive transverse myelitis, while 3 cases showed neuroimaging changes in the spinal cord as a part of acute disseminated encephalomyelitis syndrome. Cerebrospinal fluid (CSF) examinations revealed inflammatory changes in 18 patients. However, the SARS-CoV-2 virus in the CSF was discovered in 2 patients. In 2 patients, anti-SARS-CoV-2 antibodies were demonstrated in the CSF. Following treatment, 13 patients were able to walk.Conclusions: A variety of COVID-19-related spinal cord manifestations, such as acute transverse myelitis, acute necrotizing myelitis, SARS-CoV-2 myelitis, acute disseminated encephalomyelitis, neuromyelitis optica spectrum disorder, hypoxic myelopathy, MOG antibody-associated myelitis, spinal cord infarction, and spinal epidural abscess, have been reported. The possible mechanisms of this involvement being direct invasion, cytokine storm, coagulopathy, and an autoimmune response. However, response to treatment has been generally unsatisfactory, with many patients having residual weakness necessitating long-term rehabilitation.

Does Calcified Neurocysticercosis Affect Migraine Characteristics and Treatment Responsiveness? A Case-Control Study.

Recently, inflammation and free-radical release has been described in the surrounding brain parenchyma of seemingly inert calcified lesions of neurocysticercosis. These free radicals can induce migraine by stimulating calcitonin gene-related peptide release. This stipulated mechanism led us to hypothesize that calcified neurocysticercosis may increase migraine severity. This case-control study included patients (migraine with calcified neurocysticercosis) and control subjects (migraine without calcified neurocysticercosis) in a 1:1 ratio. Headache frequency, visual analog scale (VAS) score, and Migraine Disability Assessment (MIDAS) score were assessed at baseline and at the end of 3 months. To compare treatment responsiveness between patients and control subjects, we treated both groups identically so that difference in treatment would not confound the results. Each group comprised 78 patients. Baseline headache frequency (11.3 ± 3.3 versus 7.9 ± 3.4), VAS score (7.5 ± 1.1 versus 6.0 ± 1.2), and MIDAS score (15 ± 7.6 versus 9.6 ± 4.5) were significantly greater in patients than control subjects. Interestingly, the change from baseline to the end of 3 months in headache frequency (6.0 ± 1.7 versus 2.8 ± 1.4), VAS score (2.6 ± 0.02 versus 1.4 ± 0.01), and MIDAS score (8.3 ± 5.0 versus 3.6 ± 2.0) were significantly greater in patients than control subjects. Our study emphasizes that calcified lesions of neurocysticercosis are not inert, and cause an increase in the frequency and severity of migraine attacks. Interestingly, these patients also showed a better response to treatment with amitriptyline, possibly resulting from its anti-inflammatory action. Further studies are warranted to explore possible inflammatory mechanisms in calcified neurocysticercosis, which influences migraine physiology.

Alien-hand syndrome with mirror movements in hereditary diffuse leukoencephalopathy with spheroids.

Hereditary diffuse leukoencephalopathy with spheroids is a rare genetic disorder caused by mutations of the colony-stimulating factor 1 receptor gene. It is an adult-onset leukodystrophy, with a wide spectrum of neurological and psychiatric manifestations that includes Parkinsonism, dementia, seizures, limb weakness, spasticity and abnormal motor behaviour. Alien-hand syndrome and mirror movements are rare manifestations of this and other neurodegenerative disorders. We describe a woman with progressive limb and trunk rigidity, Parkinsonism and dementia, who also had involuntary left arm levitation (part of the posterior variant of alien-hand syndrome) and left-hand mirror movements. We discuss the different types of alien-hand syndrome, and the likely mechanisms of arm levitation and mirror movements.

Short course of low-dose pregabalin is effective for the treatment of restless leg syndrome in patients with cirrhosis: A pilot study.

BACKGROUND AND AIM: Restless leg syndrome (RLS) is common in patients with cirrhosis, but its treatment in such patients remains unclear. This pilot study assessed the clinical effectiveness of intravenous iron and a 6-week course of low-dose (75 mg/day) pregabalin for the treatment of RLS in patients with cirrhosis. METHODS: It was a prospective, interventional study that included adult patients with cirrhosis and RLS. The participants underwent serum ferritin measurement. Patients with low serum ferritin (< 75 µg/dL) were treated with intravenous iron. Those with normal ferritin levels and those with low levels whose RLS symptoms failed to respond to iron replacement were treated with oral pregabalin, initially 75 mg/day for 6 weeks, followed by 150 mg/day for 6 weeks if there was no response. Recurrence of symptoms was assessed at 6-12 weeks after stopping pregabalin. RESULTS: Of the 50 patients (male patients 52%; median age 48 [interquartile range: 21-65] years; median Child-Pugh-Turcotte score 8 [5-13] and median Model for End-Stage Liver disease score 17 [12-20]) studied, 29 (58%) had low ferritin; of them, 14 (48%) responded to intravenous iron alone. Eleven of 15 (38%) patients with low ferritin and nonresponse to iron, and 16 of 21 (76%) with normal ferritin levels had a response with low-dose pregabalin. Of the nine nonresponders who received 150 mg/day of pregabalin, four had to discontinue it because of adverse effects. CONCLUSION: A short course of low-dose (75 mg/day) pregabalin was effective (82%) in alleviating RLS in patients with cirrhosis. (CTRI/2019/02/017642).

Is new daily persistent headache a fallout of somatization? An observational study.

OBJECTIVE: New daily persistent headache (NDPH) is characterized by daily, persistent headache with clearly remembered onset, preceding events or triggers and treatment refractoriness of headache. The pathophysiology of NDPH is still unresolved. NDPH has been associated with somatoform disorder (DSM 4 TR). Somatization is characterized by vivid memory, disproportionate and persistent thought about symptoms that may explain many characteristics of NDPH. However, tendency towards somatization has not been studied in NDPH patients. METHODS: In this cross-sectional study, we evaluated somatization in NDPH, chronic migraine (CM), and chronic tension type headache (CTTH) by comparing the prevalence of somatic symptom disorder (SSD, DSM-5). We evaluated the past tendencies to somatization by comparing various characteristics of past somatic symptoms (number, duration, type, clearly remembered onset, etc.) between NDPH, CM, and CTTH. RESULTS: Forty-seven patients each of NDPH and CTTH and 46 patients of CM were evaluated. Criteria for SSD was fulfilled by 85.1% of NDPH and CTTH patients and only 45.7% of CM. Past history of somatic symptoms was seen in 70% patients with NDPH, 15.2% CM, and 23.4% CTTH (p<0.001). Median number of past somatic symptoms was higher in NDPH. All NDPH patients clearly remembered the onset of at least one past somatic symptom. None of CM and CTTH patients remembered the onset of past somatic symptoms. CONCLUSION: NDPH patients displayed significant past history of somatization. Continuation of past tendencies to manifest as NDPH suggests that NDPH may be an epiphenomenon of somatization.

Serum fractalkine and 3-nitrotyrosine levels correlate with disease severity in Parkinson's disease: a pilot study.

Parkinson's disease (PD) and Parkinsonian syndromes; Progressive supranuclear palsy (PSP), and Multiple system atrophy (MSA) are debilitating neurodegenerative disorders. Fractalkine is a chemokine involved in neuroinflammation, whereas, 3-nitrotyrosine (3-NT) is a marker of early neurodegenerative cellular-damage. We measured Fractalkine and 3-NT levels in the serum of these patients to examine the neuroinflammation hypothesis and also to decipher the propensity of these biologics to be used as early (5 years from onset) biochemical markers in neurodegenerative Parkinsonism. The diagnoses of PD, PSP and MSA were performed as per the respective clinical criteria. 21 PD, 9 PSP and 8 MSA patients along with controls participated in this study. Serum concentrations of Fractalkine and 3-NT were measured by ELISA. Fractalkine levels were increased in PD, PSP and MSA cohorts in comparison with controls with p < 0.001, p < 0.05 and p < 0.05 respectively. Levels of 3-NT also showed elevation in PD (p < 0.01) vs. controls. However, Pearson plot showed that Fractalkine levels were high in the patients with unified Parkinson's disease rating scale (UPDRS) part III motor score of 1, meaning slight disability, but gradually dropped in patients with motor score of 4, which is a measure of severe motor disability. This negative correlation (- .565, p < .0.01) also accentuates the neuroprotectant/anti-inflammatory nature of Fractalkine in PD. Continuous rise of 3-NT in PD, positively correlating (.512, p < 0.05) with worsening motor symptoms points to deleterious consequences of nitrosative stress. To our knowledge, this is the first report providing evidence that serum Fractalkine and 3-NT have early diagnostic/prognostic significance as PD biomarkers.

Spectrum of neurological complications following COVID-19 vaccination.

COVID-19 vaccines have brought us a ray of hope to effectively fight against deadly pandemic of COVID-19 and hope to save lives. Many vaccines have been granted emergency use authorizations by many countries. Post-authorization, a wide spectrum of neurological complications is continuously being reported following COVID-19 vaccination. Neurological adverse events following vaccination are generally mild and transient, like fever and chills, headache, fatigue, myalgia and arthralgia, or local injection site effects like swelling, redness, or pain. The most devastating neurological post-vaccination complication is cerebral venous sinus thrombosis. Cerebral venous sinus is frequently reported in females of childbearing age, generally following adenovector-based vaccination. Another major neurological complication of concern is Bell's palsy that was reported dominantly following mRNA vaccine administration. Acute transverse myelitis, acute disseminated encephalomyelitis, and acute demyelinating polyneuropathy are other unexpected neurological adverse events that occur as result of phenomenon of molecular mimicry. Reactivation of herpes zoster in many persons, following administration of mRNA vaccines, has been also recorded. Considering the enormity of recent COVID-19-vaccinated population, the number of serious neurological events is miniscule. Large collaborative prospective studies are needed to prove or disprove causal association between vaccine and neurological adverse events occurring vaccination.

18FDG-Positron Emission Tomography in patients with Tuberculous Meningitis: A Prospective Evaluation.

Lower yield of available diagnostic tests for tuberculous meningitis (TBM) frequently causes delay in diagnosis. Recently, 18F-fluorodeoxyglucose positron emission tomography (FDG PET) has been used in infectious disorders such as pulmonary tuberculosis; however, it is rarely used in TBM. This study was aimed to ascertain the role of FDG PET in the diagnosis and determination of the extent of disease and prognosis in patients with TBM. After excluding unsuitable patients, 25 patients were subjected to whole-body PET-computed tomography (CT) image acquisition along with separate brain protocol with an integrated PET-CT device. FDG PET was found to be abnormal in 92% patients. Extracranial FDG uptake was observed in 80% patients. Most common extracranial site of involvement was lymph nodes (60%), followed by lung (56%), vertebral body (8%), genitourinary organs (8%), and spleen (4%). FDG PET observed extracranial involvement had 80% sensitivity and 20% specificity in detecting definite TBM cases. In conclusion, FDG PET may be a useful test in TBM evaluation.

Paroxysmal Hemicrania: An Update.

Paroxysmal Hemicrania (PH) is classified under trigeminal autonomic cephalalgia (TAC) as per the International Classification of Headache Disorders (ICHD). Since the first description by 0ttar Sjaastad and Inge Dale in 1974, PH has been reported by many authors. A greater understanding of PH phenotype and pathophysiology has resulted in the evolution of its diagnostic criteria, and management. We tabulated major case series of PH to describe the epidemiology, clinical features and recent updates of PH. PH is a rare headache characterized by daily, multiple paroxysms of unilateral, short-lasting (mean duration <20 minutes), side-locked headache in the distribution of ophthalmic division of trigeminal nerve with associated profound cranial autonomic symptoms. Recent ICHD classification added "restlessness" to the criteria for PH. Pain should completely respond to indomethacin to fulfil the diagnostic criteria of PH. PH should be differentiated from cluster headache, SUNCT/SUNA, and other short-lasting side-locked headaches. Trigeminal afferents possibly produce pain in PH and trigeminal-autonomic reflex explains the occurrence of autonomic features. Recently, a "permissive" central role of the hypothalamus is unveiled based on functional imaging studies. Other Cox-2 inhibitors, topiramate, calcium-channel blockers, epicranial nerve blocks have been shown to improve headache in some patients of PH who cannot tolerate indomethacin. Hypothalamic deep brain stimulation has been used in treatment-refractory cases.

Neonatal Diabetes Mellitus: Novel Mutations.

OBJECTIVE: To describe the spectrum of neonatal diabetes mellitus (NDM), document new mutations, and review published Indian literature on the etiology of NDM. METHODS: Retrospective analysis of the clinical and genetic profile of 12 NDM patients. RESULTS: Eight patients presented with NDM before the age of 6 mo. Three other patients, including 2 siblings presented in later part of infancy. An additional patient was diagnosed at age 5 y with the same etiology as her infant sibling. Four patients had transient diabetes [TNDM:1 each with a mutation in KCNJ11 and INS gene, 2 with ABCC8 mutation], 7 had permanent diabetes [PNDM: 2 siblings with complete glucokinase deficiency, 2 siblings with thiamine responsive megaloblastic anemia (TRMA), 1 with Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome and 2 with Wolcott Rallison syndrome, (WRS)]. Four patients had 5 novel mutations. Genetic etiology could not be established in 1 patient with features of insulin resistance. Poorly controlled blood glucose in the TRMA patient led to hyperglycemia-induced hemichorea-hemiballismus, a rare manifestation in children. CONCLUSIONS: The authors describe 5 novel mutations, in the EIF2AK3, ABCC8, and GCK genes, a homozygous mutation at the ABCC8 locus presenting as TNDM, an obscure phenotype of the GCK gene mutation, and hyperglycemia-induced hemichorea-hemiballismus in a patient with TRMA. In India, PNDM is most commonly due to WRS similar to Middle Eastern countries with high consanguinity rates.

Encephalopathy in patients with COVID-19: A review.

Encephalopathy and encephalitis are major and devastating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus-associated central nervous system complications. Hypoxic/metabolic changes produced by intense inflammatory response against the virus triggers cytokine storm and subsequently acute respiratory distress syndrome and multiple organ failure. Hypoxic/metabolic changes result in encephalopathy. The presence of comorbidities predisposes to hypoxic/metabolic changes responsible for encephalopathy. Altered consciousness, ranging from mild confusion, delirium, to deep coma, is hallmark clinical features. Cortical and subcortical T2/FLAIR signal changes are common neuroimaging abnormalities. In a few isolated case reports of SARS-CoV-2 encephalitis, the virus has been demonstrated in cerebrospinal fluid. The presence of anosmia and ageusia can help in differentiation from other encephalopathies. We analyzed published reports on coronavirus disease 2019-associated encephalopathy. Encephalopathy is common in older patients, the majority are more than 50 years of age. The patients having encephalopathy/encephalitis are either severely or critically ill. Many patients were already on mechanical ventilation. Lung abnormalities are noted in almost all of the patients, presenting with encephalopathy. Encephalopathy is always preceded by commoner clinical features, like, fever, cough, dyspnoea, and headache. In majority, patients are already in the intensive care unit, when encephalopathy develops.

Neuromuscular presentations in patients with COVID-19.

COVID-19 is caused by the coronavirus SARS-CoV-2 that has an affinity for neural tissue. There are reports of encephalitis, encephalopathy, cranial neuropathy, Guillain-Barrè syndrome, and myositis/rhabdomyolysis in patients with COVID-19. In this review, we focused on the neuromuscular manifestations of SARS-CoV-2 infection. We analyzed all published reports on SARS-CoV-2-related peripheral nerve, neuromuscular junction, muscle, and cranial nerve disorders. Olfactory and gustatory dysfunction is now accepted as an early manifestation of COVID-19 infection. Inflammation, edema, and axonal damage of olfactory bulb have been shown in autopsy of patients who died of COVID-19. Olfactory pathway is suggested as a portal of entry of SARS-CoV-2 in the brain. Similar to involvement of olfactory bulb, isolated oculomotor, trochlear and facial nerve has been described. Increasing reports Guillain-Barrè syndrome secondary to COVID-19 are being published. Unlike typical GBS, most of COVID-19-related GBS were elderly, had concomitant pneumonia or ARDS, more prevalent demyelinating neuropathy, and relatively poor outcome. Myalgia is described among the common symptoms of COVID-19 after fever, cough, and sore throat. Duration of myalgia may be related to the severity of COVID-19 disease. Few patients had muscle weakness and elevated creatine kinase along with elevated levels of acute-phase reactants. All these patients with myositis/rhabdomyolysis had severe respiratory complications related to COVID-19. A handful of patients with myasthenia gravis showed exacerbation of their disease after acquiring COVID-19 disease. Most of these patients recovered with either intravenous immunoglobulins or steroids.