Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis.

OBJECTIVE: A large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS. METHODS: A total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis. RESULTS: Patients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively). CONCLUSIONS: The HFO amplitude in ALS is increased, but does not predict survival. SIGNIFICANCE: The enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.

Saccharopinuria accompanied by hyperammonemia and hypercitrullinemia presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia.

We report a case of saccharopinuria with hyperammonemia and hypercitrullinemia in a Japanese woman who presented with elderly-onset epilepsy, progressive cognitive decline, and gait ataxia. Blood amino acid analysis revealed an increase in citrulline, cystine, and lysine levels, and urine amino acid analysis showed increased citrulline and cystine levels. Urine metabolomics revealed an increased saccharopine level, leading to the definitive diagnosis of saccharopinuria. In western blots of liver biopsy samples, normal citrin levels were observed, suggesting that adult-onset citrullinemia type 2 (CTLN2) was not present. In addition, decreased argininosuccinate synthetase (ASS) levels were observed, and ASS1 gene, a causative gene for citrullinemia type 1 (CTLN1), was analyzed, but no gene mutations were found. Because the causes of hypercitrullinemia were not clear, it might be secondary to saccharopinuria. Muscle biopsy findings of the biceps brachii revealed diminished cytochrome c oxidase (COX) activity, mitochondrial abnormalities on electron microscopy and p62- positive structures in immunohistochemical analyses. Saccharopinuria is generally considered a benign metabolic variant, but our case showed elevated lysine and saccharopine levels causing ornithine circuit damage, mitochondrial dysfunction, and autophagy disorders. This may lead to so far unknown neurological disorders.

Midbrain atrophy related to parkinsonism in a non-coding repeat expansion disorder: five cases of spinocerebellar ataxia type 31 with nigrostriatal dopaminergic dysfunction.

BACKGROUND: Spinocerebellar ataxia type 31 (SCA31) is caused by non-coding pentanucleotide repeat expansions in the BEAN1 gene. Clinically, SCA31 is characterized by late adult-onset, pure cerebellar ataxia. To explore the association between parkinsonism and SCA31, five patients with SCA31 with concomitant nigrostriatal dopaminergic dysfunction (NSDD) development, including three cases of L-DOPA responsive parkinsonism, were analyzed. METHODS: To assess regional brain atrophy, cross-sectional and longitudinal imaging analyses were retrospectively performed using magnetic resonance imaging (MRI) planimetry. The midbrain-to-pons (M/P) area ratio and cerebellar area were measured on midsagittal T1-weighted MRI in five patients with SCA31 with concomitant NSDD (NSDD(+)), 14 patients with SCA31 without NSDD (NSDD(-)), 32 patients with Parkinson's disease (PD), and 15 patients with progressive supranuclear palsy (PSP). Longitudinal changes in the M/P area ratio were assessed by serial MRI of NSDD(+) (n = 5) and NSDD(-) (n = 9). RESULTS: The clinical characteristics assessed in the five patients with NSDD were as follows: the mean age at NSDD onset (72.0 ± 10.8 years), prominence of bradykinesia/akinesia (5/5), rigidity (4/5), tremor (2/5), dysautonomia (0/5), vertical gaze limitation (1/5), and abnormalities on 123I-ioflupane dopamine transporter scintigraphy (3/3) and 3-Tesla neuromelanin MRI (4/4). A clear reduction in the midbrain area and the M/P area ratio was observed in the NSDD(+) group (p < 0.05) while there was no significant difference in disease duration or in the pons area among the NSDD(+), NSDD(-), and PD groups. There was also a significant difference in the midbrain and pons area between NSDD(+) and PSP (p < 0.05). Thus, mild but significant midbrain atrophy was observed in NSDD(+). A faster rate of decline in the midbrain area and the M/P area ratio was evident in NSDD(+) (p < 0.05). CONCLUSION: The clinical characteristics of the five patients with SCA31 with concomitant NSDD, together with the topographical pattern of atrophy, were inconsistent with PD, PSP, and multiple system atrophy, suggesting that SCA31 may manifest NSDD in association with the pathomechanisms underlying SCA31.

Effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19).

AIM: To assess the effects of oral care on prolonged viral shedding in coronavirus disease 2019 (COVID-19) patients. METHODS AND RESULTS: We evaluated the clinical course of eight COVID-19 patients, including their duration of viral shedding, by PCR testing of nasopharyngeal swabs. The average time from the onset of symptoms until the virus was no longer detectable was 31.6 ± 11.8 days (mean ± SD; range 17-53). Thus, it took 15.1 ± 14.7 (1-40) days from the time of clinical recovery for the virus to become undetectable. In two patients who had mental retardation and psychiatric disorders, the viral shedding period continued for 44 days or 53 days. These two patients did not voluntarily brush their teeth. When they were instructed on the importance of oral care, including tooth brushing and gargling, their tests for the coronavirus became negative. CONCLUSION: Most of the patients with COVID-19 had a viral shedding period of 30 days or less. In cases of prolonged viral shedding (≥44 days), noninfectious viral nucleic acid may have accumulated in uncleaned oral cavities and continued to be detected. We propose that tooth brushing and gargling remove such viral nucleic acid and improve the accuracy of PCR testing.

Clinical characteristics of children and adults with anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVES: To investigate the clinical characteristics of children and adults with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. METHODS: Patients who tested positive for the anti-NMDAR antibody (by a cell-based assay) in the cerebrospinal fluid were enrolled. They were divided into two groups based on age (<16 years or older). RESULTS: Three children (two males and one female) and four adults (one male and three females) were examined. The age at onset was 3.0 ± 1.41 years (range: 2-5 years) for the children and 31.8 ± 6.80 years (range: 20-36 years) for the adults. The follow-up duration was 82.7 ± 23.80 months (range: 52-110 months) for the children and 61.5 ± 12.54 months (range: 43-78 months) for the adults. Prodromal symptoms such as fever and headache were observed in three adults. Two children received influenza vaccination before the onset of encephalitis. Brain magnetic resonance imaging abnormalities were observed in three children and one adult. Basal ganglia lesions were observed in two children and one adult, and the two children showed dystonia. Two children and one adult without neoplasms experienced recurrences. The modified Rankin Scale scores at the final follow-up tended to be worse in children than in adults. CONCLUSION: Three patients had basal ganglia lesions, and two of them showed dystonia. Dystonia with basal ganglia lesions has been rarely reported in anti-NMDAR encephalitis but should be noted as a significant symptom, which severely affects the activities of daily life.

The Successful Treatment of Severe Trigeminal Neuralgia by a Single Mandibular Nerve Block and Subsequent Natalizumab Administration in a Patient with Multiple Sclerosis.

We report the case of a middle-aged woman who developed trigeminal neuralgia as a sequela of multiple sclerosis (MS). The trigeminal neuralgia was refractory to medications and persisted for two years. Eventually, it was resolved by a mandibular nerve block followed by natalizumab administration. The pain was controlled for 23 months, and additional nerve blocks were not required during this period. It has been previously reported that natalizumab therapy improves the Expanded Disability Status Scale (EDSS) scores and health-related quality of life in patients with MS. In the present case, natalizumab may have prolonged the effect of the mandibular nerve block and consequently improved the patient's quality of life.