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.