Small Fiber Neuropathy: Clinicopathological Correlations.

Small fiber neuropathy develops due to the selective damage of the thin fibers of peripheral nerves. Many common diseases can cause this condition, including diabetes, infections, autoimmune and endocrine disorders, but it can occur due to genetic alterations, as well. Eighty-five skin biopsy-proven small-fiber neuropathy cases were analyzed. Forty-one (48%) cases were idiopathic; among secondary types, hypothyreosis (9.4%), diabetes mellitus (7%), cryoglobulinemia (7%), monoclonal gammopathy with unproved significance (4.7%), Sjögren's disease (3%), and paraneoplastic neuropathy (3%) were the most common causes. Two-thirds (68%) of the patients were female, and the secondary type started 8 years later than the idiopathic one. In a vast majority of the cases (85%), the distribution followed a length-dependent pattern. Intraepidermal fiber density was comparable in idiopathic and secondary forms. Of note, we found significantly more severe pathology in men and in diabetes. Weak correlation was found between patient-reported measures and pathology, as well as with neuropathic pain-related scores. Our study confirmed the significance of small fiber damage-caused neuropathic symptoms in many clinical conditions, the gender differences in clinical settings, and pathological alterations, as well as the presence of severe small fiber pathology in diabetes mellitus, one of the most common causes of peripheral neuropathy.

Quantitative analysis of gray- and white-matter volumes and glucose metabolism in Sturge-Weber syndrome.

The progressive nature of Sturge-Weber syndrome is well known, but the mechanisms of focal cortical and subcortical degeneration in this disorder are poorly understood. In the present study, we assessed the structural and functional integrity of gray and white matter in unihemispheric Sturge-Weber syndrome using quantitative magnetic resonance imaging (MRI) volumetry and MRI-based partial volume correction of [18F]fluorodeoxyglucose positron emission tomographic (PET) images. Gray- and white-matter volumes and glucose metabolism were measured in three brain regions (parieto-occipital underneath the angioma, temporal, and frontal) in six children with Sturge-Weber syndrome (two infants, ages 6 and 9 months; four older children, ages 4 to 14 years), all with unilateral parieto-occipital leptomeningeal angiomatosis. The gray-matter volumes ipsilateral to the angioma were smaller in all children, with the posterior regions underneath the angioma the most affected. In the infants, the white-matter volumes were increased in the region of the angioma, whereas in the regions remote from the angioma in the infants and in all regions of the older children, there were large decreases in white-matter volume. The decreases of frontal and temporal white-matter volume were more pronounced than the corresponding gray-matter volume decreases. The PET studies showed severe hypometabolism in the parieto-occipitalregion underneath the angioma in all of the children. However, the two infants showed glucose hypermetabolism in the frontal and temporal cortical gray matter, whereas these regions had relatively preserved metabolism in the older patients. These results demonstrate differential involvement of gray and white matter in Sturge-Weber syndrome. Both structural and functional abnormalities extend well beyond the angioma, indicating widespread abnormalities of growth and development of the affected hemisphere. Furthermore, whereas increased white-matter volume underlying the angioma may be seen in infants, ipsilateral white-matter regions outside the angioma show volume loss both in infants and in older patients. Extensive gray- and white-matter volume loss and hypometabolism ipsilateral to the angioma likely contribute to the frequently observed progressive cognitive dysfunction in these patients, regardless of the extent of the angioma.