A novel mutation in RNF216 gene in an Indian case with Gordon Holmes syndrome.

Early-onset cerebellar ataxia has a broad range of challenging differential diagnoses. Identification of hypogonadism can assist in narrowing down differential diagnosis in the presentation of progressive ataxia. Gordon Holmes syndrome as described by Sir Gordon Holmes in 1908 consists of ataxia with hypogonadism. It is due to mutation in RNF216 and OTUD4 genes which encode for enzymes in the ubiquitin-proteasome system. In this case report, we describe a 30-year-old male presenting with insidious-onset progressive ataxia with hypogonadotropic hypogonadism, cataract, pan-cerebellar atrophy with bilateral cerebral white matter hyperintensities and a positive homozygous mutation for RNF216 making the diagnosis of Gordon Holmes syndrome. The presence of hypogonadism in a patient with ataxia should alert the clinician to look for such a diagnosis.

Rhino orbital cerebral mucormycosis in settings of COVID-19 infection: A case series of thirteen patients.

Rhino orbital cerebral mucormycosis (ROCM) is an important infectious disease encountered in large numbers in this recent post-COVID-19 era. An alteration in the defense immune system during COVID-19 illness; in the presence of uncontrolled hyperglycemia has led to the new epidemic of ROCM, especially in developing nations such as India. This case series of thirteen patients illustrates the various clinical presentations, laboratory parameters, imaging features and outcomes of patients with ROCM admitted to a tertiary care hospital in Northern India. In our case series, a total of 13 newly diagnosed cases of rhino-orbital-cerebral mucormycosis were studied. A history of COVID-19 illness was observed in seven cases (53.8%) with a mean duration of mucormycosis after 25 ± 3.6 days, the use of steroids during COVID-19 illness was seen in 5 cases (38.5%), and oxygen therapy was given in 4 cases (30.8%). A comorbid state in the form of diabetes mellitus was present in 12 cases (92.3%) with a mean duration of 16.69 months, with an important finding of seven cases (53.85%) having new-onset diabetes; hypertension was present in three cases (23.1%). Magnetic resonance imaging of paranasal sinuses showed involvement of multiple sinuses in all 13 cases (100%), including maxillary and ethmoidal sinuses, with frontal involvement in 12 cases (92.3%), sphenoidal involvement in 11 cases (84.6%), symmetric involvement in 9 cases (69.2%), mastoiditis in four cases (30.8%), maxillary space involvement in four cases (30.8%), and palatal involvement in one case (7.7%). On statistical analysis, there was a significant association of new-onset diabetes, optic neuropathy and high C reactive protein with blindness (P-value < 0.05) in our study. However, there were no statistically significant association for the involvement of nervous system in our study. Multispecialty approach treatment was given in the liposomal amphotericin B therapy in all the patients along with thorough endo-nasal debridement done in all cases, transcutaneous retrobulbar amphotericin B in six cases (46.2%) with exenteration done in seven patients (53.9%). At 3 months of follow-up, there was substantial clinical improvement in all cases. There should be definite emphasis on high suspicion of mucor clinically for early diagnosis and aggressive management at the initial state of diagnosis for better outcomes. The need for sustained proper glycemic control during the COVID-19 era along with judicious use of steroids and public awareness of early symptoms and manifestations of mucor can curb the magnitude of such potentially opportunistic epidemics to a substantial rate. New-onset diabetes mellitus, optic neuropathy and high C reactive protein (>50 mg/L) showed statistically significant association with blindness. The longer the infection remains undetected, the greater the devastation ROCM can impose, of which blindness is an important hazard.

Acute Toxic Encephalopathy in Occupational Exposure with Polyvinyl Chloride (PVC) Fumes: A Case Series.

Background: Toxic encephalopathy is a spectrum of central nervous system disorders caused by exposure to toxins, especially from occupational workplace. Polyvinylchloride (PVC) is a synthetic chemical polymer that is used widely in daily activities of living. PVC is produced by polymerization of monomer units of vinyl chloride. Its manufacturing requires multiple procedures and additives for heat and light stabilization involving heavy metals. Objective: In this novel case series, we present the diverse clinical presentation of 10 patients, working in plastic recycling factory having inhalational exposure to PVC fumes, manifesting as acute toxic encephalopathy. Materials and Methods: All the patients were screened for the causes of acute encephalopathy including heavy metals, methanol poisoning, and organotins along with arterial blood gas analysis, brain imaging, and electroencephalogram. Memory loss, confusion, vertigo, headache, and nausea were complained in all the patients while seizure occurred in three patients. Neurocognitive status was grossly impaired in all the patients. Metabolic acidosis in presence of hyponatremia and/or hypokalemia was observed in nine cases. Five of the patients were having evidence of white matter involvement in brain imaging. The screening for heavy metal, methanol, and organotin were negative. Hemodialysis was done in six patients. Recovery was good in everyone and the average discharge was by 10.8 days (range: 2-25 days). All the patients were symptom-free at 3-months follow-up. Conclusion: Early suspicion and aggressive management can have favorable outcome in PVC toxic encephalopathy. Occupational hazards due to PVC toxicity are increasing in the present industrial era but it is very less identified.

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.

Extensive Vasculitis in Tuberculous Meningitis.

Tuberculous meningitis causes substantial morbidity and mortality in tropical countries. The various complications reported are hydrocephalus, vasculitic infarcts, tuberculomas, abscesses, and optochiasmatic arachnoiditis. Vasculitis in tuberculosis is basically at the level of lenticulostriate arteries supplying the basal ganglia and terminal cortical branches. In this case report, we present a rare case of tuberculous meningitis with extensive vasculopathy. During hospitalization, she developed acute onset right-sided classical hemiplegia with the inability to speak due to left internal carotid artery occlusion on imaging. The cerebrospinal fluid depicted very high protein levels. The exact pathogenesis of such extensive involvement in tuberculous meningitis substantiates the need for further studies.

Unusual association of orbital tumour and rhino-orbital-cerebral mucormycosis.

In developing tropical countries, rhino-orbital-cerebral mucormycosis has been a cause of severe morbidity and mortality during the COVID-19 pandemic. Classically, it develops as an aggressive angioinvasive destruction of nasal, orbital and cerebral involvement. Blindness is a major disabling complication. The association of mucor in cancer is linked with immunosuppression caused by radiation and/or chemotherapy. In this case report, we tried to explore the diverse possibilities of neck swelling, nasal discharge, ocular swelling and dimness of vision in a teenage boy. Rhabdomyosarcoma is a rare tumour of the soft tissue, connective tissue or bone. This type of unusual association or coexistence of rhabdomyosarcoma with mucormycetes is rarely seen in literature.