Case Report: Novel SLC9A6 Splicing Variant in a Chinese Boy With Christianson Syndrome With Electrical Status Epilepticus During Sleep

We investigated the existence and potential pathogenicity of a SLC9A6 splicing variant in a Chinese boy with Christianson Syndrome (CS), which was reported for the first time in China. Trio whole-exome sequencing (WES) was performed in the proband and his parents. Multiple computer prediction tools were used to evaluate the pathogenicity of the variant, and reverse transcription-polymerase chain reaction (RT-PCR) analysis and cDNA sequencing were performed to verify the RNA splicing results. The patient presented with characteristic features of CS: global developmental delay, seizures, absent speech, truncal ataxia, microcephaly, ophthalmoplegia, smiling face and hyperkinesis with electrical status epilepticus during sleep (ESES) detected in an electroencephalogram (EEG). A SLC9A6 splicing variant was identified by WES and complete skipping of exon 10 was confirmed by RT-PCR. This resulted in altered gene function and was predicted to be pathogenic. ESES observed early in the disease course is considered to be a significant feature of CS with the SLC9A6 variant. Combined genetic analysis at both the DNA and RNA levels is necessary to confirm the pathogenicity of this variant and its role in the clinical diagnosis of CS.

Acute Disseminated Encephalomyelitis in a 2-Year-Old Patient Following COVID-19

This report presents the case of acute disseminated encephalomyelitis in a 2-year-old patient following a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test. She presented with ataxic gait, truncal ataxia, and reduced coordination following 10 days of intermittent fever and lethargy. She did not have any respiratory symptoms. Magnetic resonance imaging of the brain and spine showed widespread T2 high signal within the gray and white matters and within the spinal cord. She was treated with intravenous methylprednisolone followed by tapering oral prednisolone; this led to resolution of her neurological symptoms. This case highlights that neurological complications can occur secondary to SARS-CoV-2 infection.

Case of acute onset ataxia caused by Klebsiella pneumoniae sepsis with the appearance of anti-GD1b antibody

Various disorders can cause acute onset ataxia including those that have toxic/metabolic, traumatic, neoplastic, vascular, demyelinating/dysmyelinating, infectious, postinfectious and genetic features. We present a case of postseptic acute ataxia. A 72-year-old woman was diagnosed with septic shock secondary to acute obstructive suppurative cholangitis. A blood sample for bacterial culture was positive for Klebsiella pneumoniae. Thus, we initiated antibiotics and intravenous immunoglobulin therapies to control the infection. We later added extracorporeal endotoxin removal with a polymyxin B immobilised fibre cartridge for endotoxin shock. The patient’s condition improved soon after endotoxin removal. Mildly slurred and explosive speech with limb and truncal ataxia, which improved gradually, developed shortly afterwards. Serum samples obtained on day 15 after admission were positive for anti-GD1b IgG antibody. The clinical course of monophasic illness with good recovery, neurological findings and the appearance of anti-GD1b antibody suggest that this case is a variant of Miller-Fisher syndrome.

Very late-onset Friedreich’s ataxia with rapid course mimicking as possible multiple system atrophy cerebellar type

This 55-year-old man was admitted to the hospital with an insidious onset, progressive backward fall (due to severe truncal ataxia), dysarthria, stiffness in extremities, distal dominant muscle wasting along with behavioural changes and urinary incontinence. Clinical assessment indicated mild cognitive decline (Mini-Mental State Examination 22/27) with cerebellar, pyramidal and peripheral nerves involvement. On investigations, nerve conduction studies revealed symmetrical, sensorimotor peripheral neuropathy affecting both lower limbs. Brain and whole spine MRI revealed widespread cerebral and mild cerebellar atrophy, pons and medulla volume loss, and a normal spinal cord. Transthoracic echocardiography revealed concentric left ventricular hypertrophy. His gene analysis revealed eight GAA repeats on allele 1, and 37 GAA repeats on allele 2 in the first intron of the frataxin gene. Considering his clinical profile and genetic analysis, he was diagnosed as a case of very late-onset Friedreich’s ataxia with likely compound heterozygous genotype.

A Homozygous Synonymous Variant Likely Cause of Severe Ciliopathy Phenotype

Joubert syndrome (OMIM #213300) is a rare neurodevelopmental disease characterized by abnormal breathing patterns, intellectual impairment, ocular findings, renal cysts, and hepatic fibrosis. It is classified as a ciliopathy disease, where cilia function or structure in various organs are affected. Here, we report a 17-year-old male whose main clinical findings are oculomotor apraxia and truncal ataxia. Magnetic resonance imaging revealed the characteristic molar tooth sign of Joubert syndrome. He also has obsessive–compulsive disorder concomitantly, which is not a known feature of Joubert syndrome. Molecular genetic analysis revealed a homozygous c.2106G>A (p.(Thr702=)) variation in the Abelson helper integration 1 (AHI1) gene and another homozygous c.1739C>T (p.Thr580Ile) variation in the coiled-coil and C2 domain-containing protein 1A (CC2D1A) gene. Even though certain AHI1 variations were previously associated with Joubert syndrome (JS), c.2106G>A (p.(Thr702=)) was only reported in one patient in trans with another known pathogenic JS variant. The CC2D1A c.1739C>T (p.Thr580Ile) variation, on the other hand, has been reported to cause autosomal recessive nonsyndromic mental retardation, but there are conflicting interpretations about its pathogenicity. Overall, to our knowledge, this is the first patient representing a severe ciliopathy phenotype caused by a homozygous synonymous AHI1 variation. Further investigations should be performed to determine any involvement of the CC2D1A gene in ciliopathy phenotypes such as Joubert syndrome.

Post-COVID Opsoclonus Myoclonus Syndrome: A Case Report From Pakistan

Background: Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory distress syndrome–coronavirus-2 (SARS-CoV-2), is primarily a respiratory infection but has been recently associated with a variety of neurological symptoms. We present herewith a COVID-19 case manifesting as opsoclonus-myoclonus syndrome (OMS), a rare neurological disorder.Case Presentation: A 63-year-old male diagnosed with COVID-19 infection developed behavioral changes, confusion, and insomnia followed by reduced mobility and abnormal eye movements within 48 h of recovery from respiratory symptoms associated with COVID-19. On examination, he had rapid, chaotic, involuntary saccadic, multidirectional eye movements (opsoclonus), and limb myoclonus together with truncal ataxia. CSF analysis, MRI of the brain, and screening for anti-neuronal and encephalitis related antibodies were negative. Extensive testing revealed no underlying malignancy. The patient was successfully treated with intravenous immunoglobulin (IVIG) with complete resolution of symptoms within 4 weeks of treatment.Conclusion: COVID-19 infection can be associated with the manifestation of opsoclonus myoclonus syndrome, a rare neurological disorder that can be treated with IVIG if not responsive to corticosteroids.

*Siringomielia asociada a Malformación de Chiari I. Reporte de caso. [Syringomyelia associated with Chiari I Malformation. Case report.]

<p>Introducción: Las Malformaciones de Chiari (M.C.) son alteraciones estructurales a nivel del cerebelo de etiología en estudio. Muy raras, afectan al 0,5% de la población. Más de la mitad de los pacientes cursan con siringomielia. Caso clínico: Femenina de 47 años con antecedente de M.C. Tipo I, acude con cuadro de dos semanas de evolución de cefalea holocraneana de intensidad 8/10, asociado a mareo e inestabilidad a la marcha. Hallazgos positivos de alteración en los pares craneales III, VIII, IX; hipertonía, signo de Babinski y Hoffman positivos bilaterales; ataxia truncal; nistagmus a la derecha; fuerza muscular disminuida en miembros superiores e hiperreflexia. Discusión: Ante la sospecha clínica, y las múltiples alteraciones a nivel del cerebelo y bulbo, se procede a realizar estudios de imagen y se confirma el diagnóstico de siringomielia.</p><p><strong>Abstract: </strong></p><p>Introduction: Chiari malformations (C.M.) are structural alterations in cerebellum. They are of unknown etiology, at present in study. They are very rare and affect 0,5 % of the population. More than half of the patients have syringomyelia. Clinical case: A 47-year-old female with medical record of C.M. Type I, presents with a two-week evolution holocranial headache, 8/10 in intensity, associated with dizziness and gait instability. Positive findings of alteration in cranial nerves III, VIII, IX; hypertonia, Babinski and Hoffman bilateral sign; truncal ataxia; nystagmus on the right; decreased muscle strength in the upper limbs and hyperreflexia. Discussion: Due to clinical suspicion and multiple alterations in cerebellum and bulb, imaging studies are performed and the diagnosis of syringomyelia is confirmed.</p>

Angel or devil? Speech disorder after dexamethasone injection for sore throat

Introduction: The use of a single-dose of intramuscular (IM) dexamethasone in emergency department (ED) is a commonly employed practice. Along with its anti-inflammatory and immunomodulatory effects, dexamethasone use has considerable adverse effects and complications that affect almost all body systems. This paper describes a middle-aged patient receiving IM injection of the agent followed by a serious temporary neurological deficit. Case report: A 48-year-old male patient presented to the ED due to cough, sore throat, fever, and malaise lasting for three days. In the medical history, the patient did not reveal any chronic illness, allergies or regular drug use. After complete evaluation, an IM injection of dexamethasone (8 mg vial) was administered to the patient as a treatment in the green (low acuity) area of the ED. While the neurological examination of the patient was completely normal on admission; dysarthria, bilateral dysmetria, and truncal ataxia ensued within 15 minutes after the IM injection. No pathological findings were detected in the laboratory and radiological work up. The signs and symptoms subsided and returned to normal within three-hour follow-up. Conclusion: Acute neurological complications, although very rare, can follow IM steroid injections. Patients receiving IM dexamethasone need to be observed for a while even if they are asymptomatic. Causal relationships need to be highlighted with well-designed prospective studies.

CSF HIV RNA Escape in Opsoclonus-Myoclonus-Ataxia Syndrome: Case Report and Review of the Literature

Background: Human immunodeficiency viruses (HIV) infection is associated with a broad range of neurological manifestations, including opsoclonus-myoclonus ataxia syndrome (OMAS) occurring in primary infection, immune reconstitution syndrome or in case of opportunistic co-infection.Case: We report the exceptional case of a 43-year-old female under HIV treatment for 10 years who presented initially with suspected epileptic seizure. Although the clinical picture slightly improved under anti-epileptic treatment, it was rapidly attributed to OMAS. The patient exhibited marked opsoclonus, mild dysarthria, upper limbs intermittent myoclonus, ataxia in 4 limbs, truncal ataxia, and a severe gait ataxia (SARA score: 34). The diagnostic work-up showed radiological and biological signs of central nervous system (CNS) inflammation and cerebral venous sinus thromboses. The HIV viral load was higher in cerebrospinal fluid (CSF) than in the blood (4,560 copies/ml vs. 76 copies/ml). She was treated for 5 days with pulsed corticotherapy. Dolutegravir and anticoagulation administration were initiated. Follow-ups at 2 and 4 months showed a dramatic improvement of clinical neurologic status (SARA score at 4 months: 1), reduction of CNS inflammation and revealed undetectable CSF and serum viral loads.Conclusion: This case underlines the importance of the evaluation of the CSF viral load in HIV patients developing OMAS and suggests CSF HIV RNA escape as a novel cause for OMAS.