Discussion and conclusions
We conducted cerebral blood flow tests and cognitive function tests over
5 years in the patient to document the disease’s slow progression. The
cognitive and behavioral symptoms exhibited by patients with
Huntington’s disease are more similar to those exhibited by patients
with frontotemporal dementia than those exhibited by patients with
Alzheimer’s disease.3 In our patient, therefore,
cerebral blood flow examination indicated Alzheimer’s-type dementia. In
general, many patients with Huntington’s disease show cognitive decline.
Over time, involuntary movements increase, and communication ability is
affected by deterioration in voluntary cognitive writing ability and
speech. Thus, the patient may understand the content of evaluator’s
questions, but involuntary movements causing dysarthria may impair
expression and communication.3 Therefore, we believe
that in patients with Huntington’s disease at old advanced age,
IMP-SPECT should be performed. Because elderly people may exhibit
different types of dementia such as Alzheimer’s-type dementia, Lewy body
dementia, and frontotemporal dementia. IMP-SPECT revealed that our
elderly female patient with Huntington’s disease also had
Alzheimer’s-type dementia.
Recently in Japan, tetrabenazine reportedly improved Huntington’s
disease-associated chorea; however, symptoms other than chorea did not
improve. Tetrabenazine depletes monoamines at nerve endings (dopamine,
serotonin, and noradrenaline) by selectively inhibiting monoamine
vesicle transporter 2 at presynaptic receptors of the central nervous
system.4 The effect of tetrabenazine on chorea results
mainly from dopamine depletion in the striatum, which is the main lesion
site of Huntington’s disease. In our patient, however, oral
administration caused nausea and fatigue, and the drug had to be
discontinued. So considering her dementia symptoms and IMP-SPCT results,
we prescribed 5 mg memantine because it has shown effects in
Alzheimer’s-type dementia.
Memantine is an N -methyl-d-aspartate (NMDA) receptor inhibitor
that is usually administered to improve cognitive function in
Alzheimer’s-type dementia5. Recently, its additional
effects such as improving swallowing function, lip dyskinesia, and
chorea-like symptoms have been reported.5 Several
patients with Huntington’s disease were administered 20 mg memantine and
ameliorating effects were observed.6 Moreover, two
memantine clinical trials are ongoing for Huntington’s
disease.7 Furthermore, it has been used for treating
other neurodegenerative diseases. The NMDA receptor antagonist
amantadine has long been used not only as an anti-parkinsonism drug but
also for treating dyskinesia.
Tetrabenazines, which are involved in the regulation of monoamine
receptors, have recently been approved by the US Food and Drug
Administration for treating tardive dyskinesia8 and
implicate a possible mechanism for chorea in Huntington’s disease.
Similarly, the administration of memantine, an NMDA receptor inhibitor,
may alleviate motor symptoms because monoamine and NMDA receptor
regulation is closely related in the brain.
In our patient, dysphagia and dysarthria were not exacerbated for 5
years after the oral administration of 5 mg memantine. Most memantine
clinical trials focusing on Huntington’s disease have been evaluations
of cognitive improvement; no detailed observational study of motor
symptoms has been conducted.7 The patient’s older
brother (II-5 in Fig. 1) developed the disease at about the same time as
her, but the disease progressed rapidly in him over 5 years; he
frequently had aspiration pneumonia and was unable to walk. Activities
of daily living were almost completely assisted. Conversely, our patient
(II-8 in Fig. 1) remained ambulatory, and she could maintain activities
of daily living to the extent that she could take a bath and use the
toilet without assistance.
Memantine has been reported to induce symptoms such as
myoclonus9; conversely, it is effective against other
motor symptoms and dystonia. One of the sites targeted by memantine is
thought to be the dysfunctional glutamatergic neurotransmitter system
via the NMDA receptor.10 In our patient, a small
amount of memantine may have been effective in slowing Huntington’s
disease progression.
Memantine was reportedly effective in a small number of Huntington’s
disease patients (Cankurtaran et al., 2006); in patients with theHTT gene who have not yet developed symptoms, memantine may
suppress symptom worsening in the future (Leavitt, 2011). Findings in
our patient suggest that oral memantine has some influence on
Huntington’s disease motor symptoms.
We recorded changes over time in 5 years, such as to be improved blood
flow image in in front-temporal lobe of IMP-SPECT. It’s treatment with
memantine prevented the progression of Clinical symptom in 5years period
of videos. We believe that this report will provide clinicians with
valuable information in diagnosing and treating Huntington’s disease.