CSF Sulfatides in Normal Pressure Hydrocephalus
October 1, 2000 4 minutes read
CSF Sulfatides in Normal Pressure Hydrocephalus
Abstract & commentary
Source: Tullberg M, et al. CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy.
J Neurol Neurosurg Psychiatry 2000;69:74-81.
Normal pressure hydrocephalus (nph) in the elderly has received increasing attention and surgical treatment in parallel with its incidence. Tullberg and colleagues present two relatively different cohorts of the disorder mainly revealed by MRI. One is a relatively idiopathic group (NPH), the other reflects a number of patients who express certain aspects of NPH but suffer from subcortical arteriosclerotic encephalopathy (SAE).
Tullberg et al present a systematic clinical and biochemical appraisal of 43 patients who fulfilled a meticulous protocol for NPH. Patients averaged 66 years old (range, 19-80 years), included 30 men and 13 women, were moderately overweight, and had a symptomatic duration of 28 months. Primary causes included previous subarachnoid hemorrhages (9); trauma (4); cerebrovascular (4); cause unknown (21); and miscellaneous (4). Clinical evaluations consisted of the following: a broad based gait disturbance; mental deterioration; enlarged, rounded ventricles on CT (2) or MRI (41); lumbar puncture pressure below 20 cm; and ventricular filling with radio-nuclide cisternography, except in patients who had aqueduct stenosis. Only patients with improved behavior after the tap test and also having a characteristic regional CBF pattern obtained by single proton emission tomography (SPECT) were accepted for shunt surgery.
Tullberg et al also describe 19 patients consisting of 13 men and six women, with a mean age of 76 years, and diagnosed SAE. Their symptoms and signs were comparable to the NPH cohort. Mean duration of symptoms was 32 months and all received MRI or high-quality CT scanning. Their mean age, however, was 10 years older than the NPH group. The large ventricles in these patients characteristically demonstrated adjacent patchy and/or periventricular hyperintensities, implying either white matter infarcts or causes similar to those found in the NPH cohort. Their symptoms and signs as well as morphological changes on MRI often resembled those in NPH, thereby presenting an important challenge to distinguish which group would be improved by ventricular shunting. Tullberg et al comment that the absence of obtaining CSF sulfatide levels may be one reason that total dependence on clinical signs alone may gain only 70% success rates in shunting "NPH."
Presurgical analysis of CSF in all patients included concentrations of the major monoamines, sulfatide, neuropeptide Y, VIP, Tau protein, ganglioside GD3, GABA and derivatives, neurofilament protein (NFL), glial fibrillary acidic protein (gFAP), neuron specific enolase, and S-100 protein. Of these, several modest differences occurred between NPH and SAE patients. But as Tullberg et al previously report (Neurology 1998;50:1122-1127), an NFL increase in the CSF of NPH patients indicates a potential capacity to reverse axonal damage. The opposite villain, as indicated here, is sulfatide, which in excess reflects a biochemical marker of progressive, nonreplaceable demyelination.
In the outcome, 34 of the 43 patients diagnosed with NPH improved after shunt surgery, two remained unchanged, and three deteriorated. Four patients said they were improved but failed to return for early follow-up evaluation. Unfortunately, detailed postoperative clinical evaluations of SAE were not available, although mortality was eventually greater in the SAE patients as indicated below.
Tullberg has graciously provided Neurology Alert with the following postoperative mortality figures of patients with or without elevated sulfatide in preoperative CSF. An elevated CSF sulfatide at or above 400 nmoL/L prior to surgery automatically characterized the patient as belonging to the SAE group. Sulfatide is the major acidic glycosphingolipid in myelin and its high level in CSF reflects sustained, continuous myelin degeneration. Of 34 patients with NPH, only two reached a CSF level of 400 nmoL/L, whereas among 19 SAE-tested patients, only four had levels just below 400 nmoL/L and the median reached 800 nmoL/L.
Within two years, four of 34 NPH patients died, one from neurofibromatosis; six of 19 SAE patients died in the same years.
Within three years, a total of five of 34 NPH patients died, compared to 10 of 19 of the SAE group.
Within five years, a total of 12 of 34 NPH patients died, as did 11 of 19 SAE.
Commentary
The absolute number of deaths in each of the two groups, NPH vs. SAE, were almost equal in this study, but the comparative qualities of the SAE cohort were measurably higher. Albeit that the SAE group averaged somewhat older ages, the statistically larger incidence of their deaths must be assigned mainly to their cerebral arteriosclerosis or some other systemic illness. Another favorable aspect of the NPH group was the careful choosing of preoperative patients lacking sulfatide in their preoperative CSF. Although numbers are small, Tullberg et al’s early follow-up included 34 such patients of whom only three worsened and one remained unchanged. Unfortunately, no careful analysis has yet been focused on the SAE groups’ functional outcomes, either postsurgically or thereafter. Neurology Alert hungers for such important information. —Fred Plum
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