Page 885 - Motor Disorders Third Edition
P. 885
MOTOR SEQUELA OF DEMENTIA / 867
were cognitive and psychiatric in 65% of patients, including 84 patients in a retrospective review (58), whereas 81%
severe alcohol and drug addiction, psychotic behavior, and patients had either cognitive change or supranuclear palsy,
suicide attempts, with motor signs occurring an average of and 42% had both. Altogether, 47% of those with cogni-
six years later, included among them atypical features such tive change had psychiatric signs of depression, euphoria,
as myoclonic head tremor and progressive cerebellar dys- anxiety, psychosis, or personality change. Other neurologi-
function. Less than one-half of the patients had fewer than cal signs, alone or in combination, in fewer than 50% of
60 CAG repeats or a known history of inheritance from an patients, included upper motor neuron signs, hypothalamic
affected parent, leading to misdiagnosis or a delay in diag- manifestations of polydipsia, hyperphagia, change in libido,
nosis of up to nine years. Preclinical HD patients have sub- amenorrhea, changes in the sleep-wake cycle, or insomnia;
stantially decreased basal ganglia and cerebral white matter 3rd, 4th or 6th cranial nerve palsies, myoclonus, ataxia,
volumes on axial-3-dimensional volumetric spoiled gradi- oculomasticatory myorhythmia (OMM), oculo-facial-skel-
ent echo MRI representing early degenerative changes (55). etal myorhythmia (OFSM), and either peripheral nervous
system (PNS) or CNS sensory deficits.
Brain FDG-PET demonstrates a decrease in glucose uti- Two reported patients with Whipple disease, confirmed
lization in cortical and striatal regions of the brain in all by positive polymerase chain reaction (PCR) for the patho-
patients with HD and in one of pre-HD patients, due to gen on serum and CSF, presented with progressive demen-
cortical abnormalities and functional deafferentation from tia confirmed by psychometric and MMSE scores in both,
saunbtacgoorntiicsatlrraedgiiootnrasc(e5r6e)l.eTmheentussetooefxDam1-,inaenddoDpa2-mreicneeprtgoicr one of whom had cortical and subcortical atrophy and
receptor binding and striatal neuronal loss show changes abnormal signal changes in periventricular white matter on
over time associated with clinical manifestations of the sTe1n-,suans dcrTit2e-rwiaeigfohrteFdTMDRiIn (59) and another that met con-
disease, including functional capacity and motor abnor- association with brain SPECT
malities. Functional brain MRI (fMRI) in HD, which is less imaging revealing regional frontal and temporal hypoper-
expensive and less invasive than FDG-brain PET imaging, fusion (60). Both patients improved clinically and neurora-
shows impaired task performance and lower task-related diologically following antibiotic therapy for up to two years.
activation in several subcortical and cortical regions while The diagnosis of WD is facilitated by tissue biopsy of the
functional connectively imaging addressing fMRI blood- small bowel, heart, brain, lymph nodes and vitreous fluid
oxygen level-dependent (BOLD) signal responses between stained with periodic acid Schiff (PAS) followed by EM
brain regions, showed impairment between anterior cin- for isolation of the bacterium; such tissues in addition to
gulated and lateral prefrontal regions and poor task per- peripheral blood and CSF are later processed by PCR for
formance associated with reduced connectivity (57). The confirmation of Whipple disease.
selective degeneration of neurons in the caudate and puta- Brain biopsy is a sensitive technique once clinical suspi-
men provide the clinicopathological correlation for chorea, cion of Whipple disease has been established, however, rec-
while intraneuronal inclusions containing huntingtin in ognizing the diagnostic accuracy of 89% for all tissue (58)
other affected cortical regions of the brain, including hip- renders it potentially unnecessary, especially when there is
pocampus, appear begin to explain behavioral and cogni- no obvious neurological involvement.
tive disturbances. Treatment of HD is aimed primarily at The neuropathological findings in Whipple disease clas-
treating depression and psychosis. sically include focally inflammatory lesions containing large
numbers of macrophages that contain PAS-positive inclu-
WHIPPLE DISEASE sions, EM of which reveal phagosomes with membranous,
laminar, or rod-shaped bacterium structures (61). False
Whipple disease, a rare systemic infectious disease, is negative results can be minimized by performing endo-
caused by infection by Tropheryma whippelii (TW), a gram- scopically guided intestinal biopsies of multiple jejunal sites
positive Actinomicetes commensal gut organism. Systemic with routine performance of EM to confirm the diagnosis.
symptoms present in the majority of patients and include If two small-bowel biopsies are not diagnostic, another
fever of unknown origin (FUO), gastrointestinal symptoms tissue should be biopsied such as lymph node, brain, or
including steatorrhea, chronic diarrhea, abdominal disten- vitreous fluid where appropriate. Brain MRI should be
sion or pain, chronic migratory arthralgia or polyarthral- performed in all suspected patients because focal abnor-
gias, and unexplained lymphadenopathy, night sweats, or malities ranging from focal lesions without mass effect to
malaise. Evidence of CNS involvement, present in about 5% large numbers of enhancing lesions with mass effect, are
of patients at presentation, eventually occurs in up to 43% noted in over one-half of patients, although they are not
of patients. Cognitive change or altered level of conscious- specific to Whipple disease.
ness without other neurological signs occurred in 11% of Criteria for the diagnosis of definite WD include the
presence of OMM or OFSM, positive tissue biopsy, and
