The varieties of psychosis in multiple sclerosis: A systematic review of cases.

OBJECTIVES: Multiple Sclerosis (MS) is known to be associated with a wide range of psychiatric symptoms, particularly with affective disorders. However, a link to psychotic disorders has not been fully established. METHODS: A systematic review of the PubMed/MEDLINE database was performed to identify cases of MS presenting with psychotic symptoms. Variables analyzed included patient demographics, clinical presentation, imaging characteristics and treatment. RESULTS: Ninety-one cases were identified. The mean age was 34.4, and there was a female predominance. The majority of patients did not have a prior history of MS or psychiatric disease. The majority of cases could be classified as having either Psychotic Disorders or Mood Disorders with psychotic features. Most patients received some type of antipsychotic therapy, with variable success. At least 26 patients were treated with corticosteroids in the acute phase of their psychotic symptoms, and the majority responded favorably. Imaging data was available for 50 patients. Of these, 60% had predominantly fronto-temporal lesions, and most had contrast enhancing lesions. CONCLUSIONS: MS can present with a variety of psychotic symptoms. The presence of enhancing lesions and steroid-responsiveness suggests these could be characterized as flares.

Branching enzyme deficiency: expanding the clinical spectrum.

IMPORTANCE: The neuromuscular presentation of glycogen branching enzyme deficiency includes a severe infantile form and a late-onset variant known as adult polyglucosan body disease. Herein, we describe 2 patients with adult acute onset of fluctuating neurological signs and brain magnetic resonance imaging lesions simulating multiple sclerosis. A better definition of this new clinical entity is needed to facilitate diagnosis. OBJECTIVES: To describe the clinical presentation and progression of a new intermediate variant of glycogen branching enzyme deficiency and to discuss genotype-phenotype correlations. DESIGN, SETTING, AND PARTICIPANTS: Clinical, biochemical, morphological, and molecular study of 2 patients followed up for 6 years and 8 years at academic medical centers. The participants were 2 patients of non-Ashkenazi descent with adult acute onset of neurological signs initially diagnosed as multiple sclerosis. MAIN OUTCOMES AND MEASURES: Clinical course, muscle and nerve morphology, longitudinal study of brain magnetic resonance imaging, and glycogen branching enzyme activity and GBE1 molecular analysis. RESULTS: Molecular analysis showed that one patient was homozygous (c.1544G>A) and the other patient was compound heterozygous (c.1544G>A and c.1961-1962delCA) for GBE1 mutations. Residual glycogen branching enzyme activity was 16% and 30% of normal in leukocytes. Both patients manifested acute episodes of transient neurological symptoms, and neurological impairment was mild at age 45 years and 53 years. Brain magnetic resonance imaging revealed nonprogressive white matter lesions and spinocerebellar atrophy similar to typical adult polyglucosan body disease. CONCLUSIONS AND RELEVANCE: GBE1 mutations can cause an early adult-onset relapsing-remitting form of polyglucosan body disease distinct from adult polyglucosan body disease in several ways, including younger age at onset, history of infantile liver involvement, and subacute and remitting course simulating multiple sclerosis. This should orient neurologists toward the correct diagnosis.

Vitamin D and multiple sclerosis.

BACKGROUND: Epidemiological data support a potential relationship between vitamin D deficiency and an increased risk of developing multiple sclerosis (MS). In vitro studies have expanded the potential role of vitamin D and its receptor beyond calcium modulation, regulation, and maintenance of bone mineralization, to include immune modulation. REVIEW SUMMARY: Whether vitamin D immunomodulatory effects can be translated into clinical benefits in MS patients is still a matter of debate. A review of the biochemistry of vitamin D and its synthesized derivatives is discussed in the context of treating vitamin D deficiency. Animal studies, which led to some human studies, are also discussed. Future studies are pending and will likely yield conclusive results as to the benefit and possible synergistic effects of vitamin D with other disease-modifying therapies of MS. CONCLUSIONS: Further prospective studies are needed to identify vitamin D levels during the various phases of MS, including relapses, remissions and progression, and to determine whether correcting vitamin D during any or all of these phases may affect the incidence or even the course of the disease.

Relationships between multiple sclerosis and depression.

The authors' findings suggest that major depressive disorder (MDD) may occur as a prodrome to and may delay diagnosis of multiple sclerosis (MS). Lifetime prevalence of MDD was 59%; 14% of subjects reported MDD as a prodrome to MS, and 10% reported a resulting delay in MS diagnosis.

Brain Accumulation of Amyloid-beta in Non-Alzheimer Neurodegeneration.

We report an unusual case of amyotrophic lateral sclerosis (ALS) marked by extensive cerebral amyloid-beta deposition in small and medium-size vessels, capillaries, and perivascular plaques in the cerebral cortex, and in most leptomeningeal vessels. Despite considerable cerebral amyloidosis, the patient remained cognitively intact until death. For comparison with other neuro-degenerative diseases and normal aging, we assessed the densities of amyloid-beta-immunoreactive cortical vessels and plaques in matched frontal and temporal lobe sections from archival uncomplicated cases of Alzheimer's disease (N=10), Pick's disease (PkD; N=4), Parkinson's disease (PD; N=6), Diffuse Lewy body disease (DLBD; N=7), progressive supranuclear palsy (PSP; N=5), multiple systems atrophy (MSA; N=4), ALS (N=7), or normal aging (N=10) by semi-quantitative grading (0 to 3+). Moderate (2+) or abundant (3+) cerebrovascular amyloid-beta immunoreactivity was detected in 8/10 AD, 3/7 DLBD, 3/6 PD, 1 each with PSP or PkD, and 2/10 controls. Moderate or abundant densities of amyloid-beta-immunoreactive diffuse plaques were detected in all cases of AD or DLBD, 4/6 with PD, 3/5 with PSP, and 2/10 controls. Moderate or abundant amyloid-beta-immunoreactive mature (dense core) plaques were present in all cases of AD or DLBD, and 3 each with PD or PSP. Importantly, amyloid-beta-immunoreactivity was not observed in the 4 MSA or 7 archival ALS cases. This study demonstrates that prominent amyloid-beta accumulation in cerebral vessels and plaques occurs frequently in AD, DLBD, PSP, and PD, but not in ALS or MSA, indicating that the case described is unique. The lack of cognitive impairment in the case presented argues against the idea that extensive amyloid-beta deposition in the brain causes dementia.