Phenotypical differences of C9ORF72 gene-positive and negative amyotrophic lateral sclerosis: a comparative case series.

BACKGROUND: Hexanucleotide repeat expansions of C9ORF72 account for a significant proportion of autosomal dominant neurodegenerative diseases in the amyotrophic lateral sclerosis (ALS)-frontotemporal dementia spectrum. In the absence of a family history, clinical identification of such patients remains difficult. We aimed to identify differences in demographics and clinical presentation between patients with C9ORF72 gene-positive ALS (C9pALS) versus C9ORF72 gene-negative ALS (C9nALS), to aid identification of these patients in the clinic and examine differences in outcomes including survival. METHODS: We retrospectively reviewed the clinical presentations of 32 patients with C9pALS and compared their characteristics with a cohort of 46 patients with C9nALS from the same tertiary neurosciences centre. RESULTS: Patients with C9pALS more commonly presented with mixed upper and lower motor signs (C9pALS 87.5%, C9nALS 65.2%; p=0.0352), but less frequently presented with purely upper motor neuron signs (C9pALS 3.1%, C9nALS 21.7%; p=0.0226). The C9pALS cohort had a higher frequency of cognitive impairment (C9pALS 31.3%, C9nALS 10.9%; p=0.0394) and bulbar disease (C9pALS 56.3%, C9nALS 28.3%; p=0.0186). There were no differences between cohorts in age at diagnosis, gender, limb weakness, respiratory symptoms, presentation with predominantly lower motor neuron signs or overall survival. DISCUSSION: Analysis of this ALS clinic cohort at a UK tertiary neurosciences centre adds to the small but growing understanding of the unique clinical features of patients with C9pALS. In the age of precision medicine with expanding opportunities to manage genetic diseases with disease-modifying therapies, clinical identification of such patients is increasingly important as focused therapeutic strategies become available.

Response to beta interferon 1b among Saudi patients with multiple sclerosis.

OBJECTIVE: To determine the efficacy and tolerability of subcutaneous beta interferon 1b (B1F1b) among Saudi patients with remitting-relapsing multiple sclerosis (R-R MS). METHODS: An open label study held at the Neurology Division of the Armed Forces Hospital, Riyadh from March 1997 until December 2001. Thirty-two consecutive patients below the age of 50 years with clinically definite R-R MS according to Poser's Criteria and expanded disability status scale below 5.5 were enrolled in treatment with subcutaneous B1F1b 8 million IU 3 times a week. The primary outcome measures used were: reduction in annual relapses, proportion of relapse-free patients, and the mean time to the first relapse after treatment was started. The secondary outcome measures used were the time to progression in disability, tolerability and safety of the beta interferon. RESULTS: Only 28 patients were analyzed to assess the outcome measures, the other 4 patients dropped out and were followed-up. Twenty were women and 8 were men (female:male ratio of 2.5:1). There was a significant reduction in relapse-rate in all patients, 32.5% were relapse-free, while 37.5% showed reduction in the number of relapses. None of our patients showed progression of disability (P<0.0249). Mild adverse reactions were seen in 38.5%, influenza-like illness occurred in 53.6%, and injection-site reaction in 35.7%. CONCLUSION: Subcutaneous B1F1b is effective in patients with R-R MS, especially in reducing relapse rate, probable disability, and it is well tolerated. However, longer follow-up is necessary to evaluate the role of B1F1b in preventing disability.

Response to beta interferon 1b among Saudi patients with multiple sclerosis.

OBJECTIVE: To determine the efficacy and tolerability of subcutaneous beta interferon 1b (B1F1b) among Saudi patients with remitting-relapsing multiple sclerosis (R-R MS). METHODS: An open label study held at the Neurology Division of the Armed Forces Hospital, Riyadh from March 1997 until December 2001. Thirty-two consecutive patients below the age of 50 years with clinically definite R-R MS according to Poser`s Criteria and expanded disability status scale below 5.5 were enrolled in treatment with subcutaneous B1F1b 8 million IU 3 times a week. The primary outcome measures used were: reduction in annual relapses, proportion of relapse-free patients, and the mean time to the first relapse after treatment was started. The secondary outcome measures used were the time to progression in disability, tolerability and safety of the beta interferon. RESULTS: Only 28 patients were analyzed to assess the outcome measures, the other 4 patients dropped out and were followed-up. Twenty were women and 8 were men (female:male ratio of 2.5:1). There was a significant reduction in relapse-rate in all patients, 32.5% were relapse-free, while 37.5% showed reduction in the number of relapses. None of our patients showed progression of disability (P<0.0249). Mild adverse reactions were seen in 38.5%, influenza-like illness occurred in 53.6%, and injection-site reaction in 35.7%. CONCLUSION: Subcutaneous B1F1b is effective in patients with R-R MS, especially in reducing relapse rate, probable disability, and it is well tolerated. However, longer follow-up is necessary to evaluate the role of B1F1b in preventing disability.

Neuromyelitis optica.

Neuromyelitis optica disease is characterized by simultaneous or successive attacks involving both the optics nerves and spinal cord without any evidence of the disease elsewhere. We report a 22-year-old Saudi woman with relapsing neuromyelitis optica disease. She had all the clinical, cerebrospinal fluid, and radiological features that differ from primary demyelinating disease. However, our patient responded well to long-term corticosteroid therapy and azathioprine with improvement in her expanded disability status scale, and ambulation. In addition, no acute relapses occurred with significant improvement on magnetic resonance imaging lesions and favorable outcome.