Pathology of roots, spinal cord and brainstem in syringomyelia-like syndrome of Tangier disease

doi:10.1016/0022-510X(91)90255-6

Journal of the Neurological Sciences

Volume 106, Issue 2, December 1991, Pages 179-185

https://doi.org/10.1016/0022-510X(91)90255-6 Get rights and content

Abstract

We report here a post-mortem examination of a 46-year-old patient who died after a 23-year-long syringomyelia-like syndrome of Tangier disease. The L5 dorsal root and the superficial peroneal nerve showed fiber loss and lipid vacuole accumulation in Schwann cell cytoplasm. The L5 ventral root had moderate fiber loss without lipid vacuoles. In the cervical roots, fiber loss was intense and there were no foamy Schwann cells. Motor neuron loss was severe in the cervical spinal cord and the facial nerve nucleus and slight at the lumbar level. Under electron microscopy, some neurons of the lower spinal cord showed atypical inclusions. These data suggest that an unknown metabolic defect is responsible for a primary neuronopathy. Lipid accumulation in Schwann cells, resulting from fiber degeneration is probably transient, accounting for the absence of foamy cells in regions with longstanding involvement.

References (26)

R.S. Kocen et al.
Familial alpha-lipoprotein deficiency (Tangier disease) with neurological abnormalities
Lancet
(1967)
R.D. Adams et al.
Neurons and neuronal reaction in disease states
P.M. Bale et al.
Pathology of Tangier disease
J. Clin. Pathol.
(1971)
J.G. Brooks et al.
Tangier disease (alpha lipoprotein deficiency)
JAMA
(1977)
P.J. Dyck et al.
Adultonset of Tangier disease, Morphometric and pathologic studies suggesting delayed degradation of neutral lipids after fiber degeneration
J. Neuropathol. Exp. Neurol.
(1978)
P.J. Dyck et al.
Pathologic alterations of the peripheral nervous system of humans
W.K. Engel et al.
Neuropathy in Tangier disease
Alpha-lipoprotein deficiency manifesting as familial recurrent neuropathy and intestinal lipid storage
Arch. Neurol.
(1967)
V.J. Ferrans et al.
The pathology of Tangier disease
A light and electron-microscopic study
Am. J. Pathol.
(1975)
D.S. Fredrickson et al.
Tangier disease: combined clinical staff conference at the National Institute of Health
Ann. Intern. Med.
(1961)
E. Gibbels et al.
Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy
J. Neurol.
(1985)

L.F. Haas et al.

Tangier disease

Brain

(1974)

H. Hager et al.

Licht und elektronen-mikroskopische sowie cytometrische Untersuchungen an peripheren Nerven bei Morbus Tangier

Acta Neuropathol. (Berl.)

(1979)

P.N. Herber et al.

Familial lipoprotein deficiency

Cited by (25)

Lipoprotein Disorders
2014, Encyclopedia of the Neurological Sciences
Lipoproteins are involved in carrying cholesterol and other lipids from the liver or intestine to plasma membranes where they interact with the adenosine triphosphate (ATP) cassette-binding transporter 1 (ABCA1) cholesterol receptor, for lipid translocation in and out of the cells. ABCA1 is the key controller of lipid homeostasis in all tissues, including the brain where cholesterol reshuffling had until the past decade escaped notice. In Tangier's disease, ABCA1 receptor mutation impairs lipid translocation that is necessary for generating high-density plasma lipoproteins. In Bassen–Kornzweig disease (abetalipoproteinemia), the mutation causes a lack of β lipoproteins that are the carriers for important dietary components such as fat-soluble vitamins.
Liver X receptor activation restores memory in aged AD mice without reducing amyloid
2011, Neurobiology of Aging
Citation Excerpt :
Increasing evidence indicates a link between AD and cholesterol metabolism (Marx, 2001; Ye et al., 2005; Hirsch-Reinshagen et al., 2008). Disturbances in cholesterol metabolism have been linked to neurological disorders such as Smith-Lemli-Opitz syndrome, Niemann-Pick disease type C, Tangier disease, Huntington's disease, and recently also to AD (Antoine et al., 1991; Tint et al., 1995; Repa et al., 2007; Milagre et al., 2008; Zhang et al., 2008). A link between cholesterol and AD is supported by the fact that APOE4, one of the three common human variants, E2, E3 and E4, is a major genetic risk factor for sporadic AD (Corder et al., 1993).
Alterations in cerebral cholesterol metabolism are thought to play a role in the progression of Alzheimer's disease (AD). Liver X receptors (LXRs) are key regulators of cholesterol metabolism. The synthetic LXR activator, T0901317 has been reported to improve memory functions in animal models for AD and to reduce amyloid-β (Aβ) deposition in the brain. Here we provide evidence that long-term administration of T0901317 to aged, 21-month-old APPSLxPS1mut mice restores impaired memory. Cerebral cholesterol turnover was enhanced as indicated by the increased levels of brain cholesterol precursors and the upregulation of LXR-target genes Abca1, Abcg1, and Apoe. Unexpectedly, the improved memory functions in the APPSLxPS1mut mice after T0901317 treatment were not accompanied by a decrease in Aβ plaque load in the cortex or hippocampus DG, CA1 or CA3. T0901317 administration also enhanced cerebral cholesterol turnover in aged C57BL/6NCrl mice, but did not further improve their memory functions.
In conclusion, long-term activation of the LXR-pathway restored memory functions in aged APPSLxPS1mut mice with advanced Aβ deposition. However the beneficial effects of T0901317 on memory in the APPSLxPS1mut mice were independent of the Aβ plaque load in the hippocampus, but were associated with enhanced brain cholesterol turnover.
Facial onset sensory and motor neuronopathy (FOSMN) syndrome responding to immunotherapies
2008, Journal of the Neurological Sciences
Citation Excerpt :
The present case fits well with their description of illness. Syringomyelia-like syndromes such as, Tangier disease [2,3], chronic sensory ataxic neuropathy with ant-disialosyl IgM antibodies [4], sarcoid neuropathy, [5], Sjogren's neuropathy [6], a pharyngeal–cervical–brachial variant of Guillain–Barré syndrome [7–9], primary amyloidosis with cranial neuropathy [10] and other conditions simulating FOSMN syndrome were excluded based on symptoms and laboratory data. A neurodegenerative process was proposed because of the absence of inflammatory cell infiltrates in the nervous tissues and the lack of response to various immunotherapies [1].
We report the first non-Caucasian case of facial onset sensory and motor neuronopathy (FOSMN) syndrome partially responding to various immunotherapies. A 55-year-old man had first felt paresthesia on his right cheek at age 45. This gradually extended to the scalp. Paresthesia of bilateral fingers and dysphagia appeared 6 years later. On admission, facial sensory impairment and bulbar palsy were found. There were no sensory or motor deficits evident in any limb, except for decreased deep tendon reflex and vibratory sensation. Videofluorography (VF) revealed decreased pharyngeal clearance. The sensory nerve action potential (SNAP) amplitudes of median and ulnar nerves were decreased. Intravenous immunoglobulin therapy and plasma exchange ameliorated his dysesthesia and dysphagia after several weeks, and resulted in improvements in VF and SNAP abnormalities. These observations suggest that FOSMN syndrome maybe, in part, immune-mediated.
Tangier Disease and Neuropathy
2005, Peripheral Neuropathy: 2-Volume Set with Expert Consult Basic
Pathology of Peripheral Neuron Cell Bodies
2005, Peripheral Neuropathy: 2-Volume Set with Expert Consult Basic
Tangier Disease and Neuropathy
2005, Peripheral Neuropathy

View all citing articles on Scopus

View full text

Research paperPathology of roots, spinal cord and brainstem in syringomyelia-like syndrome of Tangier disease

Abstract

Lancet

Neurons and neuronal reaction in disease states

Pathology of Tangier disease

J. Clin. Pathol.

Tangier disease (alpha lipoprotein deficiency)

JAMA

Adultonset of Tangier disease, Morphometric and pathologic studies suggesting delayed degradation of neutral lipids after fiber degeneration

J. Neuropathol. Exp. Neurol.

Pathologic alterations of the peripheral nervous system of humans

Neuropathy in Tangier disease

Alpha-lipoprotein deficiency manifesting as familial recurrent neuropathy and intestinal lipid storage

Arch. Neurol.

The pathology of Tangier disease

A light and electron-microscopic study

Am. J. Pathol.

Tangier disease: combined clinical staff conference at the National Institute of Health

Ann. Intern. Med.

Severe polyneuropathy in Tangier disease mimicking syringomyelia or leprosy

J. Neurol.

Tangier disease

Brain

Licht und elektronen-mikroskopische sowie cytometrische Untersuchungen an peripheren Nerven bei Morbus Tangier

Acta Neuropathol. (Berl.)

Familial lipoprotein deficiency

Research paper
Pathology of roots, spinal cord and brainstem in syringomyelia-like syndrome of Tangier disease