IRREVERSIBLE DISABILITY OCCURS AT A YOUNGER AGE IN CHILDHOOD-ONSET MS

Although childhood-onset multiple sclerosis (MS) may reach a state of irreversible disability at a slower pace than does adult-onset MS, this development, along with the conversion to secondary progression, still occurs at an age 10 years younger in childhood-onset patients than in adult-onset patients, reported researchers in the June 21 New England Journal of Medicine.

Christel Renoux, MD, a doctoral student at the McGill University Health Center in Montreal, and coinvestigators with the Adult Neurology Departments Kids with MS Study Group compared the clinical features and outcomes of a cohort of 394 patients with childhood-onset MS (onset at 16 or younger; mean age at onset, 13.7) with a group of 1,775 patients with adult-onset MS (mean age at onset, 32.2); both groups were culled from 13 centers participating in the European Database for Multiple Sclerosis network. The childhood-onset group had a significantly higher female to male ratio than did the adult-onset group, reported the researchers.

The childhood-onset group’s initial course of MS was more often exacerbating-remitting than was the adult-onset group (97.7% vs 84.3% of patients). Initial symptoms differed significantly as well: Isolated optic neuritis and isolated brain stem dysfunction were more frequent in patients with childhood-onset MS (23.4% and 16.8%, respectively), compared with rates in patients with adult-onset MS (17.9% and 8.5%, respectively); encephalitic symptoms were also observed in 7% of the childhood-onset patients, while they were “virtually absent in patients with adult-onset disease,” reported the authors. Adult-onset patients had isolated dysfunction of long tracts more frequently than did childhood-onset patients, however.

The estimated median time from MS onset to the second neurologic episode did not differ significantly between patient groups, reported Dr. Renoux and colleagues. However, median time to conversion to secondary progression was 28.1 years for the childhood-onset group, about 10 years longer than in patients with adult-onset MS. In addition, this occurred at a median age of 41.4, about 10 years earlier than in those with adult-onset MS. “The estimated median times to assignment of [Kurtzke Disability Status Scale] scores of 4, 6, and 7 were approximately 10 years longer in patients with childhood-onset MS than in patients with adult-onset MS,” the authors continued. Although the time periods between each landmark were similar in both groups, the ages at assignment for the childhood-onset patients were younger by an average of 10 years.

The authors noted that 58.6% of patients with childhood-onset MS had received one or more disease-modifying treatments, and while none of the drugs has a proven effect on the long-term disability, the authors “cannot definitively rule out an effect of treatment on the long-term course of the disease.” The research team recommended that researchers increase efforts to improve therapy for childhood-onset MS patients to match those focused on the population with adult-onset disease.

Suggested Reading
Renoux C, Vukusic S, Mikaeloff Y, et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356(25):2603-2613.

UPDATED DIAGNOSTIC CRITERIA PROPOSED FOR PROBABLE ALZHEIMER'S DISEASE

An international team of Alzheimer’s disease researchers has proposed new criteria for the diagnosis of probable Alzheimer’s disease. The updated formula uses the knowledge of the biological basis and progression of Alzheimer’s disease gained since 1984, when the existing criteria were published, according to Bruno Dubois, MD, Director of INSERM U610 at the Hôpital de la Salpêtrière, Paris, and Howard H. Feldman, MD, Professor of Neurology at the University of British Columbia, Vancouver, who led the group. Their report was published in the August Lancet Neurology.

An affected individual must first fulfill the core criterion of early episodic memory impairment. Subjective memory decline, beginning at disease onset and progressing for at least six months, and objective evidence of significant impairment of episodic memory on delayed recall testing are required. “The episodic memory impairment can be isolated or associated with other cognitive changes at the onset of Alzheimer’s disease or as Alzheimer’s disease advances,” stated the authors. A diagnosis of probable Alzheimer’s disease “cannot be established if the illness begins with a sudden onset, has focal neurological findings … or where there are seizures, gait disturbances, or extrapyramidal signs at the onset or very early in the course of the illness,” they noted. Other medical, neurologic, or psychiatric disorders must also be excluded as possible explanations of the deficits.

Under the diagnostic criteria set forth by Dr. Dubois and colleagues, at least one of four additional supportive features must also be met. They include the presence of media temporal lobe atrophy on MRI; abnormal cerebrospinal fluid biomarkers; a specific pattern in functional neuroimaging with positron emission tomography; and/or the presence of any of the identified autosomal-dominant mutations that cause Alzheimer’s disease in an immediate family member. “The proposed criteria should allow an earlier and more specific Alzheimer’s disease diagnosis than their predecessor,” said the authors. They also acknowledged the future inclusion of biomarkers that have yet to be identified and validated.

“These proposed criteria move away from the traditional two-step approach of first identifying dementia according to degree of functional disability, and then specifying its cause,” noted the authors. The investigators theorized that even before the clinical onset of symptoms, there is an Alzheimer’s disease process evolving predictably in a patient’s brain, and by the time there is a clear functional disability, it may be too late for interventions to perform optimally. “Earlier intervention with disease-modifying therapies is likely to be more effective when there is a lower burden of amyloid and hyperphosphorylated tau,” they posited.

The proposed criteria are designed to diagnose probable Alzheimer’s disease, not possible Alzheimer’s disease, due to “the incompatibility of this definition with diagnostic criteria that are highly specific for Alzheimer’s disease,” stated the authors. The researchers also recognized the need for validation of the criteria within highly specialized Alzheimer’s disease centers before they can be used in a clinical setting.           

Suggested Reading
Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol. 2007;6(8):734-746.

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