SEZ6L2 Antibody–Associated Cerebellar Ataxia Responsive to Sequential Immunotherapy

ObjectivesSeizure-related 6 homolog like 2 (SEZ6L2) antibody–associated ataxia is an extremely rare disease. Six patients have been reported and none of them improved significantly with immunotherapy. Herein, we present the case of a patient with cerebellar ataxia and SEZ6L2 antibodies who benefited from immunotherapy, which dramatically altered the course of her disease.MethodsWe present a case report of a 73-year-old woman with progressive balance problems. Her condition had rapidly deteriorated in the 2 weeks before the admission to our hospital leading to repeated falls and eventually left her bed-ridden.ResultsShe presented with severe trunk ataxia, bidirectional nystagmus, dysarthric speech, and persistent nausea. With the exception of cerebellar atrophy, extensive imaging studies revealed no pathology. SEZ6L2 antibodies were found in both CSF and serum. Over a period of 9 months, our patient received immunotherapy consisting of steroid pulse therapy, IV immunoglobulin infusions, rituximab, and cyclophosphamide. Consequently, her condition improved markedly, and she was discharged home from the neurologic rehabilitation unit.DiscussionOur case report shows that intense sequential immunotherapy may considerably improve level of functioning in some patients with SEZ6L2 antibody–associated cerebellar ataxia.Classification of EvidenceThis provides Class IV evidence. It is a single observational study without controls.

Biallelic expansion in RFC1 as a rare cause of Parkinson’s disease

An intronic expansion (AAGGG)exp in the RFC1 gene has recently been shown to cause recessively inherited cerebellar ataxia, neuropathy, and vestibular areflexia syndrome and, furthermore, a few patients with ataxia and parkinsonism have been reported. We investigated 569 Finnish patients with medicated parkinsonism for RFC1 and found biallelic (AAGGG)exp in three non-consanguineous patients with clinically confirmed Parkinson’s disease without ataxia suggesting that RFC1-related disorders include Parkinson’s disease as well.

Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature

A wide spectrum of neurodegenerative diseases has been associated with pathogenic variants in the PNPLA6 (patatin-like phospholipase domain-containing protein 6) gene, including spastic paraplegia type 39, Gordon—Holmes, Boucher—Neuhauser, Oliver—Mc Farlane, and Laurence—Moon syndromes. These syndromes present variable and overlapping clinical symptoms, encompassing cerebellar ataxia, hypogonadotropic hypogonadism, chorioretinal dystrophy, spastic paraplegia, muscle wasting, peripheral neuropathy, and cognitive impairment. In the present study, we performed a wide genetic screening in 292 patients presenting with ataxia or spastic paraplegia using a probe-based customized gene panel, covering >200 genes associated with spinocerebellar diseases. We identified six novel and four recurrent PNPLA6 gene variants in eight patients (2.7%). Six patients presented an infantile or juvenile onset (age <18), and two patients had an adult onset. Cerebellar ataxia was observed in seven patients and spastic paraplegia in one patient. Progression of cerebellar symptoms was slow in all patients, who retained ambulation even after a mean disease duration of 15 years. Brain MRI showed cerebellar atrophy in 6/8 patients, more pronounced in superior and dorsal vermis lobules (I to VII). Additional clinical features included hypogonadotropic hypogonadism (5/8), growth hormone deficiency (2/8), peripheral axonal neuropathy (4/8), cognitive impairment (3/8), chorioretinal dystrophy (2/8), and bilateral vestibular areflexia with a reduced visual vestibule-ocular reflex (1/8). In accordance with previous studies, chorioretinal dystrophy was the most frequent presenting symptom in early onset patients, hypogonadotropic hypogonadism in juvenile onset cases, and cerebellar ataxia in adult patients. One patient had an initial clinical presentation compatible with Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS), but no pathological expansions in the RFC1 gene. In conclusion, patients with PNPLA6 variants present a variable age of onset spanning from infancy to adulthood, and each clinical symptom has an age-dependent manifestation thus requiring a multi-systemic diagnostic approach. The description of patients presenting very late-onset cerebellar ataxia suggests that PNPLA6 genetic screening should also be considered in the diagnostic workout of adult cerebellar ataxia.

Cannabinoid Receptor Modulation in the 3-Acetylpyridine Cerebellar Ataxia Mouse Model

Cerebellar ataxia is a neurodegenerative disorder leading to severe motor incoordination. Recently it has been suggested that cannabinoids play a role in modulation of ataxic symptoms. In order to understand the possible therapeutic effect of cannabinoids for management of cerebellar ataxia, we used cannabinoid agonist/antagonists to target the cannabinoid type 1 receptor (CB1R) in the 3 acetyl pyridine (3AP) mouse model of ataxia. The role of the CB1R was examined by using three different doses of the CB1R agonist, WIN55,212-2 (WIN; 0.1, 0.5, 1 mg/kg) administrated 30 min prior to 3AP (55 mg/kg, i.p.) which leads to motor impairment through destruction of the inferior olive. In some recordings, the CB1R antagonist AM251(1 mg/kg) was given in combination with WIN. Locomotor activity and motor coordination were impaired by 3AP, and the application of WIN did not ameliorate this effect. However, the abnormal gait, rearing and grooming caused by 3AP were prevented by co-administration of AM251 with WIN. While the addition of the CB1R antagonist inhibition improved some ataxic symptoms, there was no effect of AM251 on balance or locomotor activity when co-administrated with WIN. Behavioral testing indicated that not only did WIN fail to exert any protective effect on ataxic symptoms, it exacerbated ataxic symptoms, suggesting that CB1R agonists may not be the ideal therapeutic drug in this disorder. When taken together, the findings from the present study indicate that cannabinoid modulation of ataxia symptoms may not act solely through CB1Rs and other cannabinoid receptors should be consider in future studies.

A Novel Coq8a Mutation in a Case with Juvenile Onset Coq10d4: Case Report and Literature Review

Primary coenzyme Q10 deficiency-4 (COQ10D4) is an autosomal recessive disorder characterized by childhood-onset of cerebellar ataxia and exercise intolerance. Molecular pathology responsible for clinical findings is mitochondrial respiratory chain dysfunction. The main clinical manifestation involves early onset exercise intolerance, progressive cerebellar ataxia and movement disorders. Some affected individuals develop seizures and have mild mental impairment, indicating variable severity. COQ8A gene mutations are responsible for this disease. Here we present a patient with tremor and cerebellar atrophy in which we detected a new mutation in the COQ8A gene. The patient's clinical findings were compatible with juvenile onset COQ10D4. Therefore, we reviewed the clinical, laboratory and genetic findings of 11 juvenile-onset COQ10D4 patients reported to date, as well as the patient's presentation.

Life of patients with cerebellar ataxia: A systematic review

Objectives: Conduct a literature search for scientific tests concerning treatment combined with well-being in cerebellar ataxias using electronic data sources. Methods: A search was conducted organized by scientific tests worried about the treatment allied to well-being in cerebellar ataxias using the electronic data sources PubMed, Medline, Embase, Cinahl and Pedro, and listings of recommendations of articles, from 1980 to December 2011, including in English and Dutch. Results: Information suggests that physical treatment, when included in occupational treatment, may improve international practical reputation, just as treatment at work alone may decrease signs of anxiety (grade 3). Conclusion: We have found some care for performing physical and work treatment, but other studies are necessary to create medical technique suggestions.

Effects of Gaze Stability Exercises with Proprioception Training to Improve Gait and Functional Independence in Cerebellar Ataxic Patients

Objective: To compare the effects of gaze stability exercises with proprioception training to improve gait and functional independence in cerebellar ataxic patients. Methods: A Quasi experimental study was conducted in the physiotherapy department in Lahore General Hospital, Lahore, Pakistan from January 2018 to June 2018.All patients were diagnosed with cerebellar ataxia and referred by neurophysician to physiotherapy department. Forty-six (46) patients were divided into two equal groups by lottery method. (Group A =proprioception training), (Group B =gaze stability with proprioception training). Data was analyzed by using statistical package for social sciences (SPSS) 21. Results: In group A, males were 13(56.5%) and females 10(43.5%) while in Group B, males were 12(52.2%) and females 11(47.8%). Mean ages were (71.3±8.47) years in Group A and (70±7.67) years in Group B. Pre and Post Functional Independence Measure (FIM)score in groups A and B with mean and standard deviation were 13.08±1.86 and 15.43±1.74 respectively. Pre and Post Timed Up and Go (TUG) test score in groups A and B with mean and standard deviation were 0.79± 0.26 and 0.97 ±0.39 respectively. Both groups were statistically significant (P value ≤ 0.05) but on the basis of mean ± standard deviation Group B method was more effective than Group A. Conclusion: Gaze stability exercises added the effects of proprioception training in improving gait and functional independence in cerebellar ataxic patients. Keywords: Cerebellar ataxia, gaze, patients, proprioception

A Case of Multiple System Atrophy (MSA) – First Presentation in a Psychiatry Service

A 67 years old female developed cognitive defficits, depression and anxiety as first symptoms of multiple system atrophy (MSA). In the course of an year autonomic failure, parkinsonism and cerebellar ataxia also developed. The case is particular because of the somatic symptoms that were initially categorised as psychogenic, the presence of confusional and vertigo episodes that were recurring but not permanent.