Familial multiple sclerosis: MRI findings in clinically affected and unaffected siblings.

Subclinical demyelinating lesions may occur in the brains of asymptomatic individuals, and the first-degree relatives of multiple sclerosis (MS) patients are at particular risk. Clinical and MRI examinations were performed in nine sibships from families with two or more cases of MS. These included 14 patients with clinically definite MS, three patients with clinically probable MS, and 27 asymptomatic siblings. Systematic criteria were applied to MRI interpretations to increase their specificity for MS. Thirteen (76%) of the 17 patients with MS showed lesions suggesting MS. Lesions were also found in six (38%) of the 16 asymptomatic siblings under age 50 and in eight (73%) of the 11 over age 50. Judged by stringent criteria, the lesions of only three (11%) of the 27 asymptomatic siblings were considered to be due to demyelination. The results demonstrate the occurrence of subclinical demyelination in asymptomatic siblings of MS patients and stress the importance of clinical follow up and MRI studies of the first-degree relatives when classifying them as healthy in family studies.     

Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment

Sixty relapsing remitting multiple sclerosis (MS) patients were selected on the basis of their score on the Fatigue Severity Scale (FSS) and formed two groups: 40 patients (fatigued MS; MSf) scored above the 75th percentile of a previously assessed representative MS sample (100 patients), and 20 age- and sex-matched patients (nonfatigued MS patients; MSnf) scored below the 25th percentile. The patients underwent clinical evaluation (Expanded Disability Status Scale (EDSS)), further assessment of fatigue (Fatigue Impact Scale), scales evaluating depression (Hamilton Depression Rating Scale (HDRS) and Beck's Depression Inventory (BDI)) and neuropsychological tests. All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction; they also underwent somatosensory evoked potentials (SSEPs) and transcranial magnetic stimulation (TMS). The patients of the MSf subgroup were then randomized to one of the following two treatments: 4-aminopyridine (4-AP) 24 mg/day and fluoxetine (FLX) 20 mg/day. After a one-week titration this treatment proceeded for 8 weeks. At the end of the treatment, EDSS, fatigue and depression scores were further evaluated. At baseline, fatigue test scores consistently correlated with depression and cognitive test scores, but not with the fatigability test. Fatigue scores decreased in both treatment groups in a similar way. Due to the design of the study, this cannot be disjoined from a placebo effect. The changes of fatigue scores could not be predicted in the FLX group, whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores.     

Familial multiple sclerosis

Siblings of patients with multiple sclerosis have an increased risk of developing the disease. In this report we describe 3 families with multiple affected members, representing the largest published aggregation of cases in first degree relatives. In the 2 families in which HLA tissue-typing was performed the affected individuals shared part of the haplotype HLA-DR2 (+ HLA-DQW1), BfS (+ C2C), C4A3, C4B1. The implications of these findings for the aetiology of multiple sclerosis are discussed.     

Quality of life in individuals newly diagnosed with multiple sclerosis or clinically isolated syndrome

Journal of Neurology - Little is known about quality of life (QOL) at the time of multiple sclerosis (MS) or clinically isolated syndrome (CIS) diagnosis and how it evolves in the critical...     

Familial Mediterranean fever and multiple sclerosis

Central nervous system (CNS) manifestations of familial Mediterranean fever (FMF) are extremely rare. These include pseudotumor cerebri, optic neuritis, CNS complications of polyarteritis nodosa type vasculitis, or hypercoagulable states secondary to renal amyloidosis, recurrent aseptic meningitis, and amyloid ophthalmoplegia. We present three patients with FMF whose neurological findings and magnetic resonance imaging (MRI) abnormalities resembled multiple sclerosis (MS). These two conditions in the same patient could arise from either coincidence or an unknown pathophysiological relationship. Both explanations are equally speculative and this matter needs further study, especially to investigate MRI features in FMF patients without CNS symptoms. Received: 2 September 1996 Received in revised form: 31 December 1996 Accepted: 6 May 1997     

The symptomatic management of multiple sclerosis

The management of multiple sclerosis (MS) revolves around disease management, symptom management, and person management. Of these, symptom management takes up the bulk of the time of the practicing physician. Some symptoms are easily managed whereas others are more difficult. Decisions have often to be made on whether to treat or to wait and watch. This article discusses the varied symptoms of MS and the approaches to management, which involves rehabilitation, pharmacological treatments, and surgical procedures. The skilled physician managing MS should be familiar with the multiple approaches to improving the quality of life of those with MS. After the diagnosis has been established and the decisions regarding treatment approaches have been made, the talk in a typical office appointment for MS usually turns to symptom management. Thus, the majority of management decisions made by the clinician revolve around that important topic. It is symptom management that will determine quality of life for those with MS, It is the basis for improving function, and, up until twenty years ago, it was the only basis for treating MS. Now, however, we can approach treatment by disease management, symptom management, and person management. The MS specialist must be well versed in all three areas.     

Huntington's disease in Venezuela: 7 years of follow-up on symptomatic and asymptomatic individuals

Persons symptomatic and at risk for Huntington's disease (HD) from a large extended family in the state of Zulia, Venezuela, have been followed prospectively for 7 years. Between 1981 and 1988, 593 people were examined, of whom 128 had symptomatic HD and 171 persons at risk had examination abnormalities that were insufficient to meet criteria for diagnosis. The remaining 294 had normal examinations. Abnormalities of saccadic eye movement and slowness of rapid alternating movements were the most common abnormalities found in at-risk individuals. Thirty persons who did not meet criteria for diagnosis at their first examination have subsequently been diagnosed with symptomatic HD. Their average age at diagnosis was 33.5 +/- 8.3 (SD) years. The likelihood of developing symptomatic HD within 3 years was 3% for those persons with normal first examinations, 23% for those with mildly abnormal first examinations, and 60% for those with highly abnormal first examinations. The rate of disease progression in early symptomatic cases were 1.4 +/- 0.1 (SEM) points per year on the Shoulson-Fahn functional capacity scale. Paternal or maternal inheritance did not appear to affect the rate of progression in this group of individuals. The data suggest that there is not a discrete age of onset but rather a prolonged period of time during which symptoms unfold.     

Familial multiple sclerosis: clinical, histocompatibility, and viral serological studies.

Evaluation of presumed "multiple sclerosis families" and comparison with recently reported families has led us to the following observations: (1) Seven of our original fourteen presumptive multiple sclerosis families had to be eliminated after personal clinical evaluation of family members failed to confirm the diagnosis in a second close relative. (2) No segregation of HLA type was noted between affected and unaffected individuals in our seven bona fide multiple sclerosis families, and no consistent segregation was noted in the twenty-eight families reported elsewhere. This supports other genetic evidence that there is not a single, major gene mapping in the HLA complex which predisposes to multiple sclerosis. (3) The DW2 antigen was increased in frequency among affected members of our families, and the A3 B7 haplotype was more frequent among affected members of other families reported. But unaffected members also tended to have an increased frequency of these same antigens. (4) No relationship was noted between HLA type and antimeasles antibody titer within our families.     

Familial multiple sclerosis: study of 357 consecutive patients

The empiric recurrence risk of multiple sclerosis (MS) of relatives of French MS patients is not known. Using a standardized interview, we collected the family histones of 357 consecutive patients followed at our MS clinic; adequate information was obtained on 4784 relatives up to the third degree. Thirty-five patients (9.8%) had a relative with MS. The risk-curve for relatives was the same as in other studies conducted with a similar methodology in Canada. England and Flanders. but the crude overall MS recurrence risk for relatives was lower in France. The genetic burden of MS may be lower in France than in areas of higher MS prevalence.     

Neurofilament levels as biomarkers in asymptomatic and symptomatic familial amyotrophic lateral sclerosis

Neurofilaments are elevated in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients. However, timing of this increase is unknown. To characterize the premanifest disease phase, we performed a cross‐sectional study on asymptomatic (n = 12) and symptomatic (n = 64) ALS mutation carriers and family controls (n = 19). Neurofilaments NF‐L (neurofilament–light chain) and pNF‐H (phosphorylated neurofilament–heavy chain) are normal before symptom onset and increased by at least an order of magnitude at early symptom onset in CSF (pNF‐H) or serum and CSF (NF‐L). Thus, blood and CSF neurofilament levels are linked to the symptomatic phase of ALS and might serve as objective markers of structural damage to the nervous system. ANN NEUROL 2016;79:152–158     

Familial clustering in Italian progressive-onset and bout-onset multiple sclerosis

Multiple sclerosis (MS) is a complex disease triggered by environmental and genetic agents, and clinically characterized by bout onset (BOMS) or progressive onset (PrMS). We collected clinical and familial aggregation data in a cohort of 518 Italian PrMS patients, and compared with 400 BOMS cases. An increased prevalence of MS in first-degree relatives of Italian PrMS was found. Familial aggregation is not influenced by probands’ clinical course, and there is no disease course concordance within MS families. These data are useful in counseling MS patients affected with different clinical courses of the disease.     

Normal conduction in pathways traversing an asymptomatic multiple sclerosis plaque.

A 31-year-old woman developed right facial myokymia as the initial manifestation of multiple sclerosis (MS). An MRI scan revealed a focal signal abnormality confined to the left dorsolateral pontomedullary region. Brain-stem auditory evoked potentials (BAEPs), somatosensory evoked potentials (SEPs), and blink reflex (BR) failed to show a conduction abnormality through the left brain-stem lesion. Instead, BAEP and BR indicated a conduction defect in the right pons and EMG showed myokymic discharges in right facial muscles. Our findings provide rare documentation of normal conduction through a presumably asymptomatic MS plaque. The abnormal MRI signal likely represents tissue edema, rather than demyelination. This case demonstrates that physical findings in MS patients may correlate better with electrophysiological abnormalities than with MRI abnormalities.     

Leukotrienes in patients with clinically active multiple sclerosis

OBJECTIVES: The role of leukotrienes (LTs) in the pathophysiology of multiple sclerosis (MS) has been controversially discussed in the past. Studies of LTs in the cerebrospinal fluid (CSF) revealed different results mainly because of analytical difficulties. MATERIAL AND METHODS: In the present study we used highly sensitive and specific analytical methods for measuring LTs in the CSF as well as in urine samples from 20 patients with active MS and 20 control patients with noninflammatory neurological disorders. RESULTS: LTB4 concentrations in CSF were almost twice as high in MS patients compared with controls (P < 0.001). CSF concentrations of the cysteinyl-LTs (LTC4, LTD4 and LTE4) as well as urinary LTE4 showed no significant differences compared with controls (P > 0.05). In addition, there was no significant association between CSF pleocytosis, clinical severity or time of disease onset. CONCLUSIONS: The increased concentration of LTB4 in the CSF of MS patients may indicate a biological importance for this mediator in MS.