The spectrum of psychiatric manifestations in subacute sclerosing panencephalitis: A systematic review of published case reports and case series.

Data related to psychiatric manifestations in subacute sclerosing panencephalitis (SSPE) is currently available only in the form of isolated case reports. In this systematic review, we evaluated the spectrum of psychiatric manifestations and their impact on the course and outcome of SSPE. Data were obtained from 4 databases (PubMed, Embase, Scopus, and Google Scholar), with the most recent search conducted on March 27, 2023. The PRISMA guidelines were followed, and the PROSPERO registration number for the protocol is CRD42023408227. SSPE was diagnosed using Dyken's criteria. Extracted data were recorded in an Excel spreadsheet. To evaluate the quality of the data, the Joanna Briggs Institute Critical Appraisal tool was employed. Our search resulted in 30 published reports of 32 patients. The mean age was 17.9 years. Schizophrenia, catatonia, and poorly characterized psychotic illnesses were the 3 most common psychiatric presentations that were seen in 63% (20/32) of cases. Catatonia was seen in 4 patients. Affective disorders, mania, and depression were reported among 22% (7/32) cases. In approximately 81% (26/32) cases, the course of SSPE was acute fulminant. Treatment with antipsychotic drugs had poor or no response. Out of 17 patients, who received antipsychotic drugs, 6 patients noted severe extrapyramidal adverse effects. SSPE often masquerades as a psychiatric disorder. Unresponsive psychiatric symptoms, early extrapyramidal signs, and progressive encephalopathy indicate SSPE.

The etiological spectrum of multiple ring-enhancing lesions of the brain: a systematic review of published cases and case series.

OBJECTIVE: Multiple ring-enhancing lesions of the brain are enigmatic neuroimaging abnormality. In this systematic review, we evaluated the etiological spectrum of these lesions. METHODS: This systematic review adhered to the PRISMA guidelines. We searched PubMed, Embase, Scopus, and Google Scholar up until 15 June 2023. We included case reports and case series. Quality evaluation of each case was based on selection, ascertainment, causality, and reporting. The extracted information included demographic characteristics, clinical features, type and number of multiple enhancing brain lesions, diagnostic procedures, final diagnoses, treatments, and patient outcomes. PROTOCOL REGISTRATION: PROSPERO CRD42023437081. RESULTS: We analyzed 156 records representing 161 patients, 60 of whom were immunocompromised. The mean age was 42.6 years, and 67% of patients experienced symptoms for up to 1 month. A higher proportion of immunocompromised patients (42% vs. 30%) exhibited encephalopathy. Chest or CT thorax abnormalities were reported in 27.3% of patients, while CSF abnormalities were found in 31.7%, more frequently among the immunocompromised. Definitive diagnoses were established via brain biopsy, aspiration, or autopsy in 60% of cases, and through CSF examination or other ancillary tests in 40% of cases. Immunocompromised patients had a higher incidence of Toxoplasma gondii infection and CNS lymphoma, while immunocompetent patients had a higher incidence of Mycobacterium tuberculosis infection and immune-mediated and demyelinating disorders. The improvement rate was 74% in immunocompetent patients compared to 52% in the immunocompromised group. CONCLUSION: Multiple ring-enhancing lesions of the brain in immunocompromised patients are more frequently caused by Toxoplasma gondii infections and CNS lymphoma. Conversely, among immunocompetent patients, Mycobacterium tuberculosis infection and immune-related demyelinating conditions are common.

Tumor Necrosis Factor-α, CD1A and CD1E Genetic Polymorphisms in Guillain-Barré Syndrome: A Study from India.

Background: Guillain-Barré Syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of peripheral nerves and roots. The pathogenesis is essentially an aberrant post-infectious immune response in a genetically susceptible host milieu. Single nucleotide polymorphisms (SNP) in genes encoding the inflammatory mediators like TNF-α, CD1A and CD1E can influence their expression and level and the susceptibility and clinical course of disease in GBS. Objective: We tried to study the susceptibility of single nucleotide polymorphisms of TNF-α and CD1 genes in Guillain-Barré Syndrome in Indian population and determine the association in terms of genotype, allele and haplotype distribution along with individual subtype, severity and clinical outcome. Methodology: In this case-control study, we investigated the single nucleotide polymorphism pattern in the promoter region of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E genes using real-time polymerase chain reaction in 75 GBS patients and analysed in comparison with 75 age and sex-matched healthy controls. Results: The findings revealed that the allelic distribution of TNF-α (-308 G/A) *A allele was associated with GBS (P value 0.04, Odds Ratio 2.03, 95% Confidence Interval 1.01-4.07). There was no association found with genotype, haplotype combination and other allele distribution for GBS in the study. CD1A and CD1E SNPs did not reveal any susceptibility for GBS. The subtype analysis did not reveal any statistical significance, except for CD1A *G allele with AMAN subtype (P value 0.026). The haplotypic combinations and mutant allele of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E were significantly associated with severe GBS in the study. However, there was no association of any SNP for mortality and survival of GBS in the study. Conclusion: TNF-α (-308 G/A)*A allele might confer genetic susceptibility for GBS in Indian population. CD1 genetic polymorphism could not be considered for susceptibility to GBS. TNF-α and CD1 genetic polymorphism did not affect mortality in GBS.

Case Report: An Unusual Case of Subacute Sclerosing Panencephalitis with Distinctive Clinical and Neuroimaging Features.

Subacute sclerosing panencephalitis (SSPE) is a relentlessly progressive brain disorder with invariable mortality. Subacute sclerosing panencephalitis is common in measles-endemic areas. We report an unusual SSPE patient with distinctive clinical and neuroimaging features. A 9-year-old boy came with a 5-month history of spontaneously dropping objects from both hands. Subsequently, he developed mental decline, a loss of interest in his surroundings, decreased verbal output, and inappropriate crying and laughing along with generalized periodic myoclonus. On examination, the child was akinetic mute. The child demonstrated intermittent generalized axial dystonic storm with flexion of upper limbs, an extension of lower limbs, and opisthotonos. Dystonic posturing was more dominant on the right side. Electroencephalography revealed periodic discharges. Cerebrospinal fluid antimeasles IgG antibody titer was markedly elevated. Magnetic resonance imaging revealed marked diffuse cerebral atrophy, and periventricular T2/fluid-attenuated inversion recovery hyperintensity. T2/fluid-attenuated inversion recovery images also revealed multiple cystic lesions present in the region of periventricular white matter. The patient was given a monthly injection of intrathecal interferon-α. The patient is currently continuing in the akinetic-mute stage. In conclusion, in this report, we described an unusual case of acute fulminant SSPE in which neuroimaging demonstrated unusual multiple small discrete cystic lesions in the cortical white matter. The pathological nature of these cystic lesions currently is not clear and needs to be explored.

Value of whole-body MRI for the assessment of response to albendazole in disseminated neurocysticercosis: a prospective follow-up study.

BACKGROUND: Disseminated neurocysticercosis is defined as simultaneous involvement of the brain (≥3 cysts) and at least one additional body site/organ. We aimed to identify disseminated cystic lesions in other body parts and investigate the effect of albendazole. METHODS: We enrolled patients with multiple (≥3) neurocysticercosis brain lesions. Whole-body MRI (short tau inversion recovery coronal sequences) was performed to assess the number of lesions in the brain and other body parts at baseline and 3 months after albendazole therapy. RESULTS: We screened 35 patients with multiple brain neurocysticercosis. In 13 patients, whole-body MRI demonstrated disseminated neurocysticercosis lesions. Ten patients were treated with albendazole. We excluded three patients. Brain MRI showed a mean lesion count of 163.6±193.8. Whole-body MRI (excluding the brain) showed a mean lesion count of 629.9±486.1. After albendazole therapy, the lesion load of the brain reduced significantly (163.6±193.8 to 99±178.3; p=0.008). Similarly, whole-body MRI showed a significant reduction in extracerebral neurocysticercosis lesion load (629.9±486.1 to 183.4±301.9; p=0.005). Three patients had complete resolution, five patients showed ≥50% reduction and two patients had <50% reduction in extracerebral lesion load. CONCLUSION: Whole-body MRI should routinely be performed in multiple neurocysticercosis lesions of the brain. Albendazole treatment leads to a remarkable reduction in neurocysticercosis lesions throughout the body.

Nerve biopsies in patients with peripheral neuropathy: A prospective evaluation.

Background: In approximately 25% of peripheral neuropathy cases, diagnosis remains obscure. In India, leprosy continues to remain one of the most frequent causes of peripheral neuropathy. We, in this prospective evaluation, performed nerve biopsies in patients with peripheral neuropathy for early confirmation of the diagnosis. Materials and Methods: A total of 55 consecutive cases of peripheral neuropathy were included in this study. All patients were subjected to clinical and electrophysiological evaluation. Sural nerve biopsies were performed in all the patients. Result: After a nerve biopsy in 29 cases, we were able to identify the underlying cause of peripheral neuropathy. In 26 cases, the diagnosis remained obscure. The most frequent histopathological diagnosis was leprosy, which was seen in 20 cases. Other diagnoses were chronic demyelinating neuropathy (four cases), vasculitis (two cases), and amyloidosis in one case. In two biopsies, the findings were consistent with hereditary neuropathies. The demonstration of lepra bacilli was the most distinctive feature. In addition, foamy macrophages (100%) and granuloma (100%) formation, epineurial (83.3%) and endoneurial infiltration (69%) along with epineurial (87.5%) and perineurial thickening (77.3%) were also noted more frequently in leprosy-associated neuropathy. Conclusion: The nerve biopsies revealed that leprosy was the most common etiology in patients with peripheral neuropathy. In approximately 47% of the cases, even nerve biopsies failed to establish a confirmed diagnosis.

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.

Tumefactive Demyelinating Brain Lesion Developing after Administration of Adenovector-Based COVID-19 Vaccine: A Case Report.

Background: Postmarketing surveillance of COVID-19 vaccination reveals that the COVID-19 vaccine administration is associated with several rare but serious neurological complications. Case Report: We report a case of new-onset tumefactive demyelinating brain lesion that developed after administration of an adenovector-based COVID-19 vaccine. A middle-aged female presented with recent right hemiparesis, which was noticed 2 days after she received the first dose of the vaccine. Magnetic resonance imaging (MRI) revealed a large subcortical T2/FLAIR hyperintensities involving corpus callosum as well. The patient responded to oral methylprednisolone. At 4 weeks, a follow-up MRI revealed a reduction in size of the lesion. Conclusion: To conclude, adenovector-based COVID-19 vaccination may be associated with a tumefactive demyelinating lesion.

Predictors of Seizure Recurrence in Solitary Calcified Neurocysticercosis in Relation to Computed Tomography Scan: Prospective Observational Study.

BACKGROUND AND PURPOSE: Solitary calcified neurocysticercosis (NCC) on the computed tomography (CT) scan of brain in patients of epilepsy is common finding in endemic regions. Factors causing seizures in such cases are debatable. Immature calcification may be the causative factor for seizure recurrence. Thus, we aimed to study predictors of seizure recurrence specific to morphological characteristics on CT scan. METHODS: Patients with solitary calcified NCC on CT scan brain and active seizures were prospectively included. The protocol included clinical evaluation, contrast-enhanced CT scan of the brain, and electroencephalogram (EEG) at baseline and 9th month of 1-year follow-up in all patients. Seizure recurrence after 1 week of enrolment was recorded. RESULTS: One hundred twenty patients with a mean age of 23.33±12.81 years were included with a final follow-up of 109 patients and 35 patients had seizure recurrence. On univariate analysis, seizure frequency of more than 1 episode/month (45.7% vs. 25.7%, p=0.037; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.05-5.68), perilesional edema on CT head (45% vs. 10.8%, p<0.001; OR, 6.95; 95% CI, 2.58-18.7), lower density (HU) of lesion on CT head (139.85±76.54 vs. 204.67±135.9 HU p=0.009) and abnormal EEG at presentation (p<0.001; OR, 18.25; 95% CI, 2.15-155.13) were significantly associated with seizure recurrence. On multivariate analysis, presence of perilesional edema on CT head (p=0.001; OR, 6.854; 95% CI, 2.26-20.77), density of lesion on CT (HU) (p=0.036; OR, 0.995; 95% CI, 0.99-1) and abnormal EEG (p=0.029; OR, 12.125; 95% CI, 1.29-113.74) were independently associated with seizure recurrence. CONCLUSIONS: The presence of perilesional edema, HU of calcification on CT brain, and abnormal EEG suggest an increased risk of seizure recurrence in patients of epilepsy with solitary calcified NCC.

The Multiple Cranial Nerve Palsies: A Prospective Observational Study.

BACKGROUND: Neurological presentation with isolated multiple cranial nerve palsies is common and its diverse causes include infectious, neoplastic, and inflammatory pathologies. The aetiological spectrum may depend upon geographical regions. We undertook this study to explore clinical spectrum and aetiological profile of multiple cranial nerve palsies. METHODS: This hospital-based prospective observational study was conducted from August 2015 to August 2017. All the consecutive patients of multiple cranial palsies presenting to the neurology department were included in the studies. Primary objectives were to define anatomical syndromes/cranial nerve combinations and to establish aetiology. Secondary objectives were to study associated factors. The multiple cranial nerve palsy was defined as involvement of two or more non-homologous nerves. Patients of neuromuscular junction disorders, anterior horn cell disorders, myopathies, brain stem syndromes were excluded. All patients underwent structured protocol of clinical evaluation, investigations and few specialized investigations in accordance with clinical suspicion to establish the diagnosis. RESULTS: Fifty-four patients with a mean age of 39.9 ± 14.2 years were included. Commonest cranial nerve involved was the abducens (75.9%) among all nerve combinations. The cavernous sinus syndrome (37%), orbital apex syndrome (22.2%) and jugular foramen syndrome (11.1%) were the most frequent anatomical patterns. Infections (40.7%) were the commonest aetiology followed by neoplastic and idiopathic in four patients. CONCLUSION: Cavernous sinus syndrome was the commonest anatomical syndrome of multiple cranial nerve palsies and infections were the commonest cause in this study.

Extra-central nervous system tuberculosis in HIV-uninfected patients of tuberculous meningitis: A prospective evaluation.

OBJECTIVE: Disseminated tuberculosis is characterized with involvement of two or more non-contiguous sites. In this work we evaluated patients of tuberculous meningitis for possible extra-central nervous system tuberculosis. METHOD: This prospective observational study was performed at a tertiary care institute in Northern India. We included consecutive HIV-uninfected cases of TBM. Patients were evaluated for extra-central nervous system (CNS) tuberculosis. We focussed on peripheral lymph nodes, chest, abdomen, and spinal involvement. All patients were subjected to MRI brain and spine. Patients were also subjected to CT thorax and abdomen. Enlarged lymph nodes, if present, were biopsied. Ascitic and pleural fluid were subjected to biochemical, cellular analysis as well as cartridge-based nucleic acid amplification test (CBNAAT) for detection of Mycobacterium tuberculosis and rifampicin resistance. RESULTS: We enrolled 110 patients of TBM. After cerebrospinal fluid examination alone, 14 (12.7%) patients had microbiologically-confirmed TBM. After planned work-up for extra CNS tuberculosis, 5 additional cases were microbiologically confirmed. Similarly, before work-up for extra CNS tuberculosis, 29 (26.4%) patients were categorized as probable TBM. The number of probable cases increased to 72 (65.5%) (P<0.001) with identification of tuberculosis elsewhere. Lung (83.6%) was the most involved site. Abdominal tuberculosis was noted in 29 (26.4%) patients. On imaging spine, 17 (15.5%) patients demonstrated presence of spinal tuberculous. Lymph adenopathy recorded in 2 cases. Lymph node biopsy revealed tuberculous granuloma in both the cases. All 7 patients, who died, had disseminated tuberculosis. CONCLUSION: Extra CNS tuberculous involvement is common in TBM. Search for extra CNS tuberculous enables upgrading diagnostic accuracy.

Pathological, ultrasonographic, and electrophysiological characterization of clinically diagnosed cases of pure neuritic leprosy.

A subset of neuritic form of leprosy, called pure neuritic leprosy (PNL), seen in a minority of leprosy patients, is characterized by peripheral neuropathy without skin lesions and an absence of acid-fast bacilli on skin smears. Patients with PNL are often started on drug therapy without confirmation of diagnosis. We, therefore, did a prospective study of clinically diagnosed PNL patients with correlation of ultrasonographic and biopsy findings. A total of 100 consecutive patients with PNL, diagnosed according to the consensus case definition, were included in the study. All patients underwent nerve conduction study, peripheral nerve ultrasonography, and sural nerve biopsy. Multiple mononeuropathies were present in 75% of cases, mononeuropathy in 18%, and polyneuropathy in the remaining 7%. Compared to clinical examination, ultrasonographic assessment of the peripheral nerves was not only better at the detection of thickening but also helped in characterization of their fascicular architecture, echogenicity, and vascularity. A total of 32 cases were confirmed on nerve biopsy, out of which 75% had demonstrable lepra bacilli. Cranial nerve involvement, presence of trophic ulcers, and bilateral thickening of the great auricular nerve were significantly associated with the positivity of lepra bacilli. A significant improvement in the disability score happened after multidrug therapy. A comprehensive electrophysiologic, ultrasonographic, and histological evaluation may be helpful in establishing a diagnosis of PNL with greater confidence, while ruling out other non-leprosy diagnoses.

Quantitative assessment of lesion load and efficacy of 3 cycles of albendazole in disseminated cysticercosis: a prospective evaluation.

BACKGROUND: The management of disseminated cysticercosis is unclear and largely considered hazardous. The role of albendazole remains controversial in such patients. METHODS: A tertiary care, University hospital-based prospective intervention study was conducted from December 2015 to December 2017. Patients with disseminated cysticercosis, defined as the presence of multiple viable neurocysticerci (≥ 3) in the brain along with involvement of an additional extra site, were included in the study. Patients with cysticercal encephalitis were excluded. A detailed evaluation, including ophthalmoscopy, ocular B scans, ultrasound abdomen, and X-rays were done. Albendazole was administered at a dose of 15 mg/kg/day in 3 cycles of 28 days each. All patients were also given adjuvant corticosteroids and anti-epileptic drugs. Clinical and radiological follow up was carried out at a difference of 3 months between each treatment cycle. For radiological quantification, lesions were counted at 10 pre-specified levels. Statistical analysis was done to estimate the difference in seizure frequency and lesion load. RESULTS: Twenty-nine patients (21 with > 20 lesions; 8 with ≤ 20 lesions) were given albendazole as per the protocol. There was a significant reduction in the occurrence of seizures (P < 0.001) and headache (P < 0.001). A significant reduction in lesion load from baseline to third follow-up was seen in the estimations done at different levels (P < 0.001). No patient developed serious side-effect warranting cessation of therapy. CONCLUSION: Cyclical use of albendazole appears efficacious in treating disseminated cysticercosis. The method of quantification described may be used in future studies for objective assessment. TRIAL REGISTRATION: ISRCTN11630542; 28th September 2019; Retrospectively registered.

Why do neurologists miss catatonia in neurology emergency? A case series and brief literature review.

Catatonia is a well-described clinical syndrome characterized by features that range from mutism, negativism and stupor to agitation, mannerisms and stereotype. Causes of catatonia may range from organic brain disorders to psychiatric conditions. Despite a characteristic syndrome, catatonia is grossly under diagnosed. The reason for missed diagnosis of catatonia in neurology setting is not clear. Poor awareness is an unlikely cause because catatonia is taught among conditions with deregulated consciousness like vegetative state, locked-in state and akinetic mutism. We determined the proportion of catatonia patients correctly identified by neurology residents in neurology emergency. We also looked at the alternate diagnosis they received to identify catatonia mimics. Twelve patients (age 22-55 years, 7 females) of catatonia were discharged from a single unit of neurology department from 2007 to 2017. In the emergency department, neurology residents diagnosed none of the patients as catatonia. They offered diagnosis of extrapyramidal syndrome in 7, meningitis in 2, and conversion reaction, acute psychosis/encephalopathy and non-convulsive status epilepticus in one each. Their final diagnosis at discharge was catatonia due to general medical condition in 6 (progressive supranuclear palsy in 2, post-status epilepticus, uremic encephalopathy, glioblastoma multiforme and tuberculous meningitis in one each), catatonia due to major depression in 4, schizophrenia and idiopathic catatonia in one each. Extrapyramidal syndrome appeared as common mimic of catatonia. The literature reviewed also revealed the majority of organic catatonia secondary to causes that are usually associated with extrapyramidal features. Therefore, we suggest that neurologists should consider catatonia in patients presenting with extrapyramidal syndromes.

Atypical frontal lobe seizure as the first manifestation of gall-bladder cancer: a case report.

BACKGROUND: Gall bladder cancer (GBC) is associated with abdominal pain, lump, nausea, vomiting, and jaundice due to either gall bladder mass or the involved adjacent peritoneal structures. Gall bladder cancer presenting as refractory epilepsy is rare. Here we report a young female GBC patient who presented with an atypical and refractory frontal lobe seizures as the first manifestation of gall bladder cancer. CASE PRESENTATION: A 46 years young female presented first time to the hospital with uncontrolled seizures and headache in 5 months duration. Seizures were very atypical in semiology with ptosis and mydriasis to either side along with ipsilateral ocular deviation. The episodes were bilateral but right eyelid ptosis, mydriasis and right horizontal conjugate deviation were frequent. MRI brain showed encephalomalacia in the left frontal region on axial T2 and coronal T1 weighted images without any enhancement on gadolinium contrast. CECT abdomen revealed a heterogeneously enhancing gall bladder mass with the evidence of lung metastasis from chest CT scan. CSF for malignant cytology was negative. Seizures were refractory to the treatment. CONCLUSION: Though CNS involvement is uncommon but it can be the only presentation in gall bladder cancer.