Journal of Neurology, Neurosurgery, and Psychiatry 1982;45:271-273

Short report

Familial cerebellar ataxia with cerebrovascular
amyloid
S LOVE, LW DUCHEN
From the Department of Neuropathology, Institute of Neurology, The National Hospital, Queen Square,
London

SUMMARY We report a rare association of familial cerebellar ataxia (without dementia) and cerebrovascular amyloid. Postmortem neuropathological examination of one member of the family
showed amyloid angiopathy of the central nervous system with heavy infiltration of capillaries in the
hippocampus and cerebellum.
Cerebrovascular amy!oid occurs in a number of
Examination disclosed mild, symmetrical cerebellar
clinical contexts and may be an asymptomatic ataxia of the limbs and trunk with a slurring dysarthria
finding in the elderly.' Patients may develop demen- and nystagmus on lateral gaze. The blood pressure was
tia and the risk of cerebrovascular accidents is 120/70 mm Hg while lying supine. Haematological and
increased.2 There are known associations of amyloid biochemical investigations, including thyroid function
were normal. No abnormalities were noted on
angiopathy with Alzheimer's disease3 and spongi- tests, skull
and cervical spine radiographs. A Wasserman
chest,
form encephalopathy.4 To our knowledge, cerebellar test was negative.
The ataxia worsened progressively so
ataxia with cerebrovascular amyloid has previously that within
two years she could not walk without support.
been reported in only one family in which affected Three years after her first presentation she developed
members became demented early in the course of sudden weakness and stiffness of the left lower limb.
Tone
the illness.5 6 The present report is of cerebrovascular was increased in that limb, with left ankle clonus and
amyloid affecting one member of a family in which bilateral extensor plantar responses. Sensation was
four members in three successive generations devel- intact. An electroencephalogram was diffusely abnormal;
irregular, intermittent 11 Hz alpha rhythm was present
oped cerebellar ataxia without dementia.
with a left-sided emphasis and irregular 15 Hz activity
occurred with a right-sided emphasis. A brain scan
Case report
was normal. Progressive incapacitation led to her adMrs IB, a 49-year-old housewife, presented with slight mission to a home for the physically handicapped.
unsteadiness of gait. She gave no history of alcohol in- During her last few months of life she became incontinent
of urine and, for the first time, impairment of memory
gestion, exposure to carbon monoxide, previous head for
recent events was noted, although she remained
injury or encephalitis, and was taking no medication.
Her maternal grandfather had been bedridden with orientated and lucid. She died ten years after the onset of
"unsteady limbs" for 9 years prior to his death. One her illness, at the age of 59 years.
maternal uncle died following a cerebral haemorrhage,
and two maternal uncles suffered from cerebellar ataxia Neuropathological findings Consent was obtained for a

post mortem examination limited to the central nervous
system. The external appearance of the brain and spinal
cord was normal. The unfixed brain weighed 1240 g.
After fixation the cerebrum was sectioned coronally.
The lateral and third ventricles were slightly dilated. Two
Address for reprint requests: Dr S Love, Department of
Neuropathology, Institute of Neurology, The National slit-like, small infarcts were present in the white matter
of the right frontal and temporal lobes. No abnormalities
Hospital, Queen Square, London WC1N 3BG, UK.
were seen in the brain stem, cerebellum or spinal cord.
Received 24 September 1981 and in revised form 11 November Blocks were taken from many areas of the cerebral
1981
hemispheres, brain stem, cerebellum and spinal cord.
Accepted 18 November 1981
In the cerebral hemispheres and leptomeninges, arteries
271

with nystagmus. Eleven other maternal aunts and uncles
as well as the patient's mother died from unrelated illnesses. Two siblings are believed to be healthy.

272

Love, Duchen

and arterioles were diffusely thickened by eosinophilic,
acellular material with affinity for Congo red and
showing yellow-green birefringence under polarised
light thus fulfilling the criteria for amyloid.7 8In many
areas the lumen was narrowed and in places amorphous
deposits of amyloid extended for short distances into the
surrounding brain parenchyma. Scanty deposits were
present in the tunica media of some veins. Involvement of
capillaries was virtually restricted to the hippocampal
formation where amyloid infiltrated capillary walls,
occasionally occluding the lumen, and radiating
spicules of amyloid extended into the surrounding
parenchyma. These deposits were not argyrophilic with
either the Glees and Marsland or Palmgren method of
silver impregnation. In addition, numerous neuritic
(senile-type) plaques were present in the dentate fascia, Fig 1 Section shows cerebellar molecular layer.
hippocampal formation and subiculum but nowhere else Capillaries are infiltrated by amyloid which extends as
: .:
........
in the cortex, and many hippocampal pyramidal cells spicules into surrounding
Congo
neuropil.
contained neurofibrillary tangles or granulovacuolar red-haematoxylin x 290.
inclusions. The presence of old infarcts in the white
matter was confirmed. The basal ganglia and brain stem
showed widespread arterial amyloid, capillaries being
spared.
The cerebellum was extensively infiltrated by large
deposits of amyloid, many of which were clearly related
to capillaries (fig 1). These deposits were numerous in the
molecular and granule cell layers and a few were present
in the white matter. Generalised arterial amyloid was
present in the cerebellum and overlying leptomeninges.
There was severe depletion of Purkinje cells and many
"torpedoes" were noted on axons of those surviving
(fig 2). The granule cells were relatively well preserved.
The molecular layer showed Bergmann cell hyperplasia
and there was nerve fibre loss and gliosis in the white
matter. Arterial amyloid was present throughout the
spinal cord and in the spinal leptomeninges with only Fig 2 Section shows cerebellar Purkinje cell layer. A
occasional capillary involvement in the white matter. torpedo is present on the axon of a degenerating
There was a rim of nerve fibre loss in the subpial white Purkinje cell. There is also evidence ofPurkinje cell
matter of the cervical region. The nerve roots showed no loss. Glees and Marsland silver impregnation x 270.
vascularamyloid and no other pathological abnormalities.
1
:

Discussion
Worster-Drought, Greenfield and McMenemey
described a family with presenile dementia, spastic
paraplegia, ataxia of gait and nystagmus.5 6 Postmortem examination of two members showed
generalised "hyaline" arterial wall thickening and
argyrophilic pericapillary deposits (later confirmed
to be amyloid) most numerous in the hippocampal
formation and cerebellum, but also involving the
pons and medulla. Neuritic plaques and neurofibrillary tangles were present in the hippocampal
cortex, and the cerebellum showed some loss of
Purkinje cells with "torpedoes" on axons of surviving cells. Their case, unlike the present one,
showed widespread white matter degeneration and
gliosis. Although atypical "kuru" plaques have been
described in other progressive neurological diseases

with cerebellar ataxia,9 10 vascular amyloid has not
been present.
In the family described by Worster-Drought et al,
dementia was a prominent feature. This may reflect
the extensive white matter changes and, possibly,
more severe hippocampal damage. The patient
reported here remained lucid and alert until her
death, and no other family members became
demented. However, ataxia of gait and nystagmus
were common to both families, with almost identical
appearance and distribution of the cerebrovascular
amyloid. Familial cerebellar ataxia, with or without
dementia, appears, therefore, to be a further
manifestation of cerebrovascular amyloid, which is
associated with microvascular amyloid in the
hippocampus and cerebellum.

Familial cerebellar ataxia wvith cerebrovascular amyloid
References
Wright JR, Calkins E, Breen WJ, Stolte G, Schultz RT.
Relationship of amyloid to aging. Review of the
literature and systematic study of 83 patients derived
from a general hospital population. Medicine
(Baltimore) 1969 ;48 :39-60.
2 Okazaki H, Reagan TJ, Campbell RJ. Clinicopathologic studies of primary cerebral amyloid angiopathy.
Mayo Clin Proc 1979;54:22-31.
Mandybur TI. The incidence of cerebral amyloid
angiopathy in Alzheimer's disease. Neurology (NY)
1975;25:120-6.
Adam J, Crow TJ, Duchen LW, Scaravilli F, Spokes E.
Familial cerebral amyloidosis and spongiform
encephalopathy. J Neurol Neurosurg Psychiatry 1982;
45:237-245.
5 Worster-Drought C, Greenfield JG, McMenemey WH.
A form of familial presenile dementia with spastic

273
paralysis (including the pathological examination of
a case). Brain 1940 ;63 :237-54.

6 Worster-Drought C, Greenfield JG, McMenemey WH.
A form of familial presenile dementia with spastic
paralysis. Brain 1944;67:38-43.
Cooper JH. Selective amyloid staining as a function of
amyloid composition and structure. Lab Invest
1974 ;31 :232-8.
8 Glenner GG, Eanes ED, Bladen HA, Linke RP,
Termine JD. a-pleated sheet fibrils. A comparison of
native amyloid with synthetic protein fibrils. J
Histochem Cytochem 1974;22:1141-58.
Gerstmann J, Straussler E, Sheinker I. Uber eine
eigenartige hereditar-familiare Erkrankung des
Zentralnervensystems. gesamte Neurol Psychiatr
1936 ;154 :736-62.
Boellaard JW, Schlote W. Subakute spongiforme
Encephalopathie mit multiformer Plaquebildung.
Acta Neuropathol 1980;49:205-12.