Central and peripheral nervous system dysfunction in the clinical variation of Salla disease.

OBJECTIVE: To evaluate the degree of possible peripheral nervous system (PNS) involvement in addition to CNS manifestations in Salla disease, a free sialic acid storage disorder leading to severe mental retardation with a wide clinical variation. BACKGROUND: Salla disease is a lysosomal storage disorder that affects the white matter of the CNS. MRI findings and recent 1H MRS study results provide evidence for delayed central myelination, but there is no previous evidence for PNS involvement in this disease. The gene coding for a presumptive sialic acid transport protein has recently been identified, and the first disease-causing mutations have been characterized. METHODS: Nerve conduction studies; evoked potentials to visual (VEP), brainstem auditory (BAEP), and somatosensory stimuli (SEP); and EEG were carried out on 22 patients (age range 2 months to 57 years) with biochemically and genetically confirmed Salla disease. Brain MRI were available on 14 patients. RESULTS: Nerve conduction studies revealed abnormalities in nearly half of the patients (10/21). The four severely disabled patients and the oldest patient had greatly reduced nerve conduction velocities and prolonged distal latencies compatible with demyelinating polyneuropathy. In addition, SEP was abnormal in the majority of the patients, but VEP and BAEP in only a few cases. PNS involvement was clearly associated with both the phenotypic severity and MRI findings. CONCLUSIONS: The results indicate that dysmyelination in Salla disease occurs not only in the CNS but also in the peripheral nervous system, contributing to the phenotypic variation, which can now be correlated with the molecular basis of the disease.

A new metabolite contributing to N-acetyl signal in 1H MRS of the brain in Salla disease.

OBJECTIVE: To determine whether N-acetylaspartate (NAA) is reduced in patients with Salla disease, a neurodegenerative disorder. BACKGROUND: 1H MRS allows the brain metabolism to be studied noninvasively in vivo. N-acetyl (NA) is composed primarily of NAA, which is regarded as a neuronal marker. The NA signal in 1H MRS is reduced in several neurodegenerative disorders. Increased NA signal has thus far only been found in Canavan's disease as a result of NAA accumulation in the brain tissue. In Salla disease, an autosomal recessive free sialic acid storage disorder, N-acetylneuraminic acid (NANA), accumulates in lysosomes of brain tissue. METHODS: The authors studied eight patients with Salla disease (age range, 6 to 44 years) and eight age-matched healthy volunteers using quantitative 1H MRS. The spectra were obtained from two selected 8-cm3 volumes of interest localized in the basal ganglia and in the parietal white matter using conventional 1.5-T MRI equipment. The spectral resonance lines of NA groups, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed quantitatively. All MR images were evaluated to verify the state of myelination. RESULTS: 1H MRS from parietal white matter revealed 34% higher NA and 47% higher Cr concentrations, and a 35% lower Cho concentration in the patients with Salla disease compared with the age-matched control subjects. The patients had a 22% higher water content in their parietal white matter, whereas in the basal ganglia the water concentrations did not differ significantly. In the patients' basal ganglia the Cr concentration was 53% higher. CONCLUSIONS: NAA is considered to be a neuronal marker that, except for Canavan's disease, has been found or assumed to be either stable or reduced. However, in Salla disease the high NA signal may have a contribution from accumulated lysosomal NANA, which offsets the possible loss of NAA. The high Cr is in line with the increased glucose uptake found in our earlier 2-fluoro-2-deoxy-D-glucose-PET study, reflecting increased energy demand. It is worth noting that in a conventional 1H MRS ratio-based analysis these underlying abnormalities would have remained undetected. Our study thus emphasizes the importance of a quantitative assessment of metabolite concentrations in 1H MRS for detecting altered brain metabolism.

Brain involvement in Salla disease.

BACKGROUND AND PURPOSE: Our purpose was to document the nature and progression of brain abnormalities in Salla disease, a lysosomal storage disorder, with MR imaging. METHODS: Fifteen patients aged 1 month to 43 years underwent 26 brain MR examinations. In 10 examinations, signal intensity was measured and compared with that of healthy volunteers of comparable ages. RESULTS: MR images of a 1-month-old asymptomatic child showed no pathology. In all other patients, abnormal signal intensity was found: on T2-weighted images, the cerebral white matter had a higher signal intensity than the gray matter, except in the internal capsules. In six patients, the white matter was homogeneous on all images. In four patients, the periventricular white matter showed a somewhat lower signal intensity; in five patients, a higher signal intensity. In the peripheral cerebral white matter, the measured signal intensity remained at a high level throughout life. No abnormalities were seen in the cerebellar white matter. Atrophic changes, if present, were relatively mild but were found even in the cerebellum and brain stem. The corpus callosum was always thin. CONCLUSION: In Salla disease, the cerebral myelination process is defective. In some patients, a centrifugally progressive destructive process is also seen in the cerebral white matter. Better myelination in seen in patients with milder clinical symptoms.

Increased brain glucose utilization in Salla disease (free sialic acid storage disorder).

UNLABELLED: Salla disease is an autosomal recessive lysosomal free sialic acid storage disorder characterized by psychomotor retardation and ataxia. MRI studies have revealed evidence of dysmyelination, but the biological mechanism of the brain dysfunction is unknown. METHODS: Nine patients with Salla disease (age 2.5 mo-42 y) presenting the disease in varying degrees of severity were studied by PET using 2-fluoro-2-deoxy-D-glucose (FDG) as a tracer. Local cerebral metabolic rates for glucose (LCMRGlc) in individual brain regions were compared with controls. RESULTS: The FDG PET results showed significantly increased LCMRGlc values in the frontal and sensorimotor cortex and especially in the basal ganglia of the patients. Cerebellar hypometabolism was present in all seven patients with marked ataxia, whereas the less severely affected patients without obvious ataxia had normal or even high glucose uptake in the cerebellum. CONCLUSION: The increased cerebral glucose utilization is a constant finding in Salla disease and may reflect the basic defect of the sialic acid metabolism in this disorder. The FDG PET findings in the cerebellum suggest a correlation between glucose uptake and the severity of the clinical symptoms.

Twenty-six early operations in brachial birth palsy.

26 babies with brachial birth palsy were operated on at the age of 12-275 days (mean 75 days) in paediatric surgical departments of Helsinki (12 cases) and Turku (14 cases) University Central Hospitals during years 1970-1985 using microsurgical techniques. Epineuroraphy was used in 9, interfascicular nerve grafting in 7, neurolysis in 7, and intercostal neurotisation in 3 cases. The functional status of the upper extremity was recorded 1 to 14 years after the operation using a modified Mallet's classification: 6 were good, 17 fair and 3 poor. The outcome after epineuroraphy was similar to interfascicular grafting. One intercostal neurotisation resulted in fair function and 2 in poor, but the result in target function, i.g. in the peripheral neurotised nerve, was good.