Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia

Background: There is no authorized treatment for ataxia telangiectasia (AT). As cerebellar symptoms of storage diseases were improved by acetyl-DL-leucine (ADLL), the authors hypothesized a symptomatic and disease-modifying effect in AT upon supplementation with ADLL. Methods: Six patients were treated with ADLL 3 g/day for 1 week followed by 5g/day for 3 weeks to 1 year. Cerebellar ataxia was evaluated by validated scales. Gaze-holding, saccades and smooth pursuit were examined by video-oculography. Measurements took place at baseline, at 1 month of therapy in 5 patients, and after 6 and 12 months in 1 patient. Results: The Scale for Assessment and Rating of Ataxia changed from the baseline, mean, (SD, min-max) of 22.1 (5.88, 11-28.5) to 18 points (5.39, 8.5-23.5) after 1 month on medication ( P = .0028). All patients demonstrated gaze-holding deficits; 3 patients had central-position downbeat-nystagmus. Mean slow-phase velocity of this nystagmus with the gaze straight-ahead changed from 5.57°/s (1.8, 3.53-6.99) to 4.7°/s (0.79, 3.97-5.56) after 1 month on treatment (1.35, -2.56-4.17) ( P = .046). Interpretation: ADLL may improve ataxia and ocular stability in AT patients, while the molecular basis still remains to be elucidated. A multicentric, rater-blinded, phase II trial currently investigates the effects of acetyl-L-leucine in AT (NCT03759678).

Lambert-Eaton Myasthenic Syndrome Presenting as Cerebellar Symptoms

A 79-year-old man visited neurology clinic due to gait ataxia and vertigo for 10 months. Neurologic examination revealed saccadic pursuit, mild dysmetria, impaired tandem gait, and areflexia that recovers after exercise. The amplitude of compound muscle action potentials recorded on the abductor digiti minimi increased up to 6,639.4% during repetitive nerve stimulation at 50 Hz stimulation. This case demonstrates that clinicians should consider Lambert-Eaton myasthenic syndrome as a differential diagnosis when a patient complains of gait ataxia and vertigo.

CACNA1A-p.Thr501Met mutation associated with familial hemiplegic migraine: a family report

Background and aims Hemiplegic migraine (HM) is a rare form of migraine characterized by the presence of a motor and other types of aura. HM can be sporadic or familial. Familial hemiplegic migraine (FHM) is an autosomal dominant disorder, classified into 3 subtypes, based on the gene involved (CACNA1A in FHM1, ATP1A2 in FHM2 and SCN1A in FHM3). The clinical presentation is highly heterogeneous and some attacks may be severe. We report the clinical characteristics and genetic analysis of 12 patients belonging to a family with CACNA1A-p.Thr501Met gene mutation. Methods We screened for mutations in CACNA1A gene 15 patients belonging to the same family. The exonic sequences of CACNA1A were analyzed using a Tru-seq® Custom Amplicon (TSCA) (Illumina Inc., San Diego, CA) targeted capture and paired end library kit. Sanger sequencing was used to confirm CACNA1A variants and segregation analysis. Results CACNA1A-p.Thr501Met mutation was found in 12 of the 15 patients screened, which was compatible with the diagnosis of FHM1. Attacks of hemiplegic migraine were reported by 10 of the 12 subjects (83.33%). Only one subject developed persistent mild cerebellar symptoms and none of the subjects developed cerebellar atrophy. Discussion The variant p.Thr501Met was described previously in association with episodic ataxia and rarely with FHM related to cerebellar symptoms. FHM1 has a broad clinical spectrum and about half of the families have cerebellar involvement. In our study, only one patient developed persistent cerebellar deficits. These data suggest that CACNA1A-p.Thr501Met mutation can occur prevalently as hemiplegic migraine.

Radiosurgical treatment of patients with intracranial pilocytic astrocytomas

The study objective is to assess the outcomes after stereotactic radiosurgical treatment (SRS) in patients with pilocytic astrocytomas after non-radical surgery and after continued tumor growth.Materials and methods. The report includes 56 patients (37 males and 19 females) who have undergone SRS in N. N. Burdenko National Medical Research Center of Neurosurgery from March 2005 to January 2018.Results. The majority of patients (75 %) were children. Almost 43 % of patients underwent SRS as part of the primary treatment after biopsy or incomplete removal, other patients – in the event of continued tumor growth after non-total surgery. Tumors involved the cerebellum (41 %), brainstem (23 %), thalamus (19.6 %) and cerebral hemispheres (16.1 %). The median tumor volume was 1.9 cm3 (0.14–19.00 cm3), 23 % of patients had cysts in the tumor. The prescribed dose was 12 to 22 Gy (median 18 Gy) over 50–80 % isodose line. The follow-up was available for 54 (96.4 %) patients. The median follow-up was 67 months (3–151 months). All patients were alive at the end of the follow-up examination. In 14 (25 %) patients, the development of pseudo-progression (PSP) was noted. The median detection of PSP is 11 months (3–65 months). Of these, in 7 (50 %) patients PSP was accompanied by clinical deterioration: in 5 – an increase in general cerebral symptoms and in 1 patient – an episode and an increase in cerebellar symptoms. Eight (57 %) patients with PSP were reoperated: 4 underwent removal of the tumor, 4 – emptying of the cyst and placement of the Ommaya reservoir, which led to regression of the existing symptoms. No other toxicity was observed in patients. At the time of the completion of the follow-up examination (with a given median follow-up), no relapses were detected. There was no clinical deterioration after SRS.Conclusion. Radiosurgical treatment is an effective and safe method of radiation treatment for patients with primary pilocytic astrocytomas and recurrent pilocytic astrocytomas, providing control over tumor growth in all patients with a low risk of complications.

Long-term Implication of Metronidazole Induced Reversible Cerebellar Toxicity and Peripheral Neuropathy- A Case Report

Metronidazole Induced Encephalopathy (MIE) is rare and serious central nervous system toxicity. A 40-year-old male, on long-term self treatment with metronidazole (cumulative dose: 102 gm) presented with dysarthria, nystagmus, unsteadiness, and numbness in both legs. A Magnetic Resonance Imaging (MRI) scan of the brain revealed a symmetric hyperintensity in both the dentate nuclei of cerebellum on both T2 weighted and Fluid-Attenuated Inversion-Recovery (FLAIR) imaging. Discontinuation of metronidazole resulted in resolution of the imaging findings and clinical improvement occurred within one month. Metronidazole-induced neurotoxicity should be considered in patient who present with cerebellar symptoms and characteristic lesion on MRI in close temporal relation with metronidazole intake and drug should be discontinued to prevent permanent neurological deficit.

Long-term Implication of Metronidazole Induced Reversible Cerebellar Toxicity and Peripheral Neuropathy- A Case Report

Metronidazole Induced Encephalopathy (MIE) is rare and serious central nervous system toxicity. A 40-year-old male, on long-term self treatment with metronidazole (cumulative dose: 102 gm) presented with dysarthria, nystagmus, unsteadiness, and numbness in both legs. A Magnetic Resonance Imaging (MRI) scan of the brain revealed a symmetric hyperintensity in both the dentate nuclei of cerebellum on both T2 weighted and Fluid-Attenuated Inversion-Recovery (FLAIR) imaging. Discontinuation of metronidazole resulted in resolution of the imaging findings and clinical improvement occurred within one month. Metronidazole-induced neurotoxicity should be considered in patient who present with cerebellar symptoms and characteristic lesion on MRI in close temporal relation with metronidazole intake and drug should be discontinued to prevent permanent neurological deficit.

Body lateropulsion as the primary manifestation of medulla oblongata infarction: a case report

Background Isolated body lateropulsion is a possible predominant manifestation of medulla oblongata infarction, and can occur without vestibular and cerebellar symptoms. However, it is relatively rare and challenging to diagnose. Case presentation A 67-year-old woman was admitted to the Harris International Peace Hospital complaining mainly of instability when standing and walking for the previous 8 hours. Based on the neural localization and multiple head magnetic resonance imaging (MRI) examinations, a diagnosis of cerebral infarction (vertebrobasilar system) was made. Consequently, the patient was managed using therapy aimed at preventing platelet aggregation, lowering plasma lipids, stabilizing plaques, protecting mitochondria, and improving circulation and brain function. The patient’s gait improved and she was discharged after 14 days because she was able to walk unaided. The patient was followed up for 6 months and had no noticeable undesirable side effects or signs of neurological deficits. Conclusion The possibility of lateral medulla oblongata infarction should be considered when patients present with isolated body lateropulsion, without other signs or symptoms of brainstem damage.

Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia

Objective: Friedreich’s ataxia (FRDA) is the most common hereditary ataxia. It is a neurodegenerative disorder, characterized by progressive ataxia. FRDA is also associated with cognitive impairments. To date, the evolution of cognitive functioning is unknown. Our aim was to investigate the changes in the cognitive functioning of FRDA patients over an average eight-year timeframe. In addition, we aimed to study the relationship between cognitive changes and clinical variables. Methods: Twenty-nine FRDA patients who had been part of the sample of a previous study participated in the present study. The mean average time between the two assessments was 8.24 years. The participants completed an extensive battery of neuropsychological tests chosen to examine cognitive functioning in various cognitive domains: processing speed, attention, working memory, executive functions, verbal and visual memory, visuoperceptive and visuospatial skills, visuoconstructive functions and language. Results: At follow-up, cerebellar symptoms had worsened, and patients presented greater disability. Differences between baseline and follow-up were observed in motor and cognitive reaction times, several trials of the Stroop test, semantic fluency, and block designs. No other cognitive changes were observed. Deterioration in simple cognitive reactions times and block designs performance correlated with the progression of cerebellar symptoms. Conclusions: Our study has demonstrated for the first time that patients with FRDA experience a significant decline over time in several cognitive domains. Specifically, after an eight-year period, FRDA patients worsened in processing speed, fluency, and visuoconstructive skills. This progression is unlikely to be due to greater motor or speech impairment.

Clinical-genealogical and molecular-genetic features of spinocerebellar ataxia type 1 in the Khabarovsk Region

The clinical picture of SCA1 in the Khabarovsk Region is characterized, along with cerebellar symptoms, by more frequent manifestations of pyramidal, extrapyramidal, cognitive, autonomic and psychiatric disorders. The age of patients was 34,1 ± 4,2 years, and the age of disease onset was 31,4 ± 2,3 years. The number of CAG-repeats in the ATXN1 gene varied from 43 to 63. The non-mutated ATXN1 gene in the Khabarovsk Region population contained 29,0 ± 0,4 CAG-repeats. The prevalence of SCA1 in the Khabarovsk Region was 1:100 000 of the population which corresponds to the world prevalence of 1–3:100 000 of the population.