Spinocerebellar ataxia type 4 (SCA4): Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-12-19

AUTHORS

Y. Hellenbroich, K. Gierga, E. Reusche, E. Schwinger, T. Deller, R. A. I. de Vos, C. Zühlke, U. Rüb

ABSTRACT

Summary.Spinocerebellar ataxia type 4 (SCA4), also known as ‘hereditary ataxia with sensory neuropathy’, represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases. More... »

PAGES

829-843

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00702-005-0362-9

DOI

http://dx.doi.org/10.1007/s00702-005-0362-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050084197

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16362839


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34 schema:description Summary.Spinocerebellar ataxia type 4 (SCA4), also known as ‘hereditary ataxia with sensory neuropathy’, represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.
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41 schema:keywords CAG repeats
42 Purkinje cell layer
43 abducens
44 addition
45 affected nuclei
46 analysis
47 area
48 ataxia
49 auditory
50 auditory brainstem nuclei
51 auditory impairment
52 autopsy cases
53 brainstem auditory
54 brainstem degeneration
55 brainstem fibers
56 brainstem neurodegeneration
57 brainstem nuclei
58 brainstem tissue
59 cases
60 cell layer
61 central nervous regions
62 central raphe
63 cerebellar
64 cerebellar ataxia
65 cerebellar fastigial nucleus
66 cerebellum
67 clinicopathological study
68 concept
69 course
70 degeneration
71 demyelinization
72 diplopia
73 disease
74 disease symptoms
75 dorsal column nuclei
76 dorsal motor vagal
77 dysphagia
78 explanation
79 face
80 fastigial nucleus
81 fiber tracts
82 fibers
83 findings
84 form
85 function
86 functional role
87 gaze-evoked nystagmus
88 help
89 hereditary ataxias
90 hypoglossal
91 hypoglossal nucleus
92 immunocytochemical analysis
93 immunocytochemical study
94 immunoreactivity
95 impairment
96 inferior olive
97 interpositus
98 investigation
99 lack
100 lateral reticular nucleus
101 lateral vestibular
102 layer
103 loss
104 marked neuronal loss
105 medial subnuclei
106 members
107 nervous regions
108 neurodegeneration
109 neuronal loss
110 neuropathy
111 nigra
112 nucleus
113 nucleus of Roller
114 nucleus raphe interpositus
115 nystagmus
116 olive
117 pathoanatomical study
118 patients
119 polyglutamine diseases
120 pons
121 pontine nuclei
122 postmortem investigations
123 potential
124 prepositus hypoglossal nucleus
125 present findings
126 present study
127 pursuit
128 raphe
129 raphe interpositus
130 region
131 results
132 reticular nucleus
133 reticulotegmental nucleus
134 role
135 roller
136 saccadic smooth pursuit
137 sections
138 sensory neuropathy
139 serial thick sections
140 severe neuronal loss
141 smooth pursuit
142 somatosensory function
143 spinocerebellar ataxia type 4
144 study
145 subnuclei
146 substantia nigra
147 superior vestibular
148 symptoms
149 tegmental area
150 thick sections
151 time help
152 tissue
153 tract
154 type 4
155 untreatable form
156 vagal
157 ventral tegmental area
158 vestibular
159 view
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