Huntington's disease (HD), a relentlessly progressive neurodegenerative disorder, is characterized by a clinical triad of psychiatric, cognitive and motor disturbances. The antibiotic minocycline, a caspase inhibitor exhibiting antiapoptotic properties, has been shown to prolong survival in the transgenic mouse model of HD. We administrated minocycline to 14 patients with genetically confirmed HD. The patients were psychiatrically, neurologically and neuropsychologically evaluated at baseline, and after 6 and 24 months of treatment, using the Unified HD Rating Scale and a neuropsychological test battery. After 12 months, three patients were lost to follow-up so that 11 patients were analysed at the endpoint. Minocycline was well tolerated. Unlike the expected natural course of HD, patients exhibited stabilization in general motor and neuropsychological function at endpoint, after improving in the first 6 months. Moreover, we found a significant amelioration of psychiatric symptoms that was not apparent after the first 6 months. In detail, the Mini-Mental State Examination, the Total Motor Score, the Total Functional Capacity Scale and the Independence Scale, as the most prominent scales in HD, were stabilized after 3 years of treatment. Our results confirm previous animal studies and indicate a neuroprotective effect of this agent in HD. A long-term, double-blind, placebo-controlled trial appears highly warranted for definitively establishing the value of minocycline in HD.

This is the largest study on apraxia in HD. Ideomotor limb apraxia is a common sign in HD patients, occurring in a high percentage. In contrast to the opinion of several authors, occurrence of apraxia in HD is independent from neuropsychological decline and the severity of most neurological symptoms.

Reference 1. Friedman JH. More on repetitive behaviors in Parkinson's disease. Mov Disord 2005;20:509. Huntington's Disease and MinocyclineWe read with interest the brief report by Thomas and colleagues 1 on their open-label study of 28 Huntington's disease (HD) patients on minocycline. The patients were rated at baseline and after 6 months using the Unified HD Rating Scale (UHDRS), the Mini-Mental State Examination, and the Abnormal Involuntarily Movement Scale. In contrast to our results in an earlier, similarly designed study, 2 they could not find a significant change in one of these scales. However, this finding might be the result of adding together the four main parts of the UHDRS, which in our view is somewhat misleading. The UHDRS 3 is divided into four components assessing motor performance, cognition, behavior, and functional capacity. The motor component consists of 31 questions rated on a 0to 4-point scale, with 4 indicating the most severe impairment. The five-item cognitive component consists of the Benton Verbal Fluency Test, 4 the Symbol Digit Modalities Test, 5 and the Stroop Test. 6 The behavioral assessment consists of 28 items assessing severity and frequency of mood, anxiety, aggression, psychosis, and other behavioral abnormalities. The functional component is composed of three subunits: first, the functional checklist, which includes 25 yes/no questions; the second is the Independence Scale 7 ; and the third is the Total Functional Capacity Scale. 8 Whereas the motor part and the behavioral assessment indicates a greater number as greater impairment, all three neuropsychological tests, the functional checklist, the independence scale, and the total functional capacity scale, do the opposite, thus indicating a lower number as greater impairment. So what exactly do the authors mean by a UHDRS mean value of 235.8 units? The maximal point count is 124 units for the UHDRS motor part, 25 units for the psychosocial function, 13 units for the functional capacity, 100 units for the independence scale, whereas cognitive parameters do not have an upper limit.We encourage the authors to share the details of this important study with the community. This is not just of academic interest, as there are data on the natural course of a variety of UHDRS subtests, which makes it possible to evaluate the value of minocycline in HD. Siesling and coworkers examined 78 patients 9 and found the motor component of the UHDRS to be deteriorated by 5.97 units per year. More data are available on the natural course of the Independence Scale: Siesling reported a decline of 3.6 units per year, the Huntington Study Group (960 patients) 10 found a declined at a rate of 4.5 units, and Myers and colleagues 7 found a 5.3 units decrease for the same period. On the other hand, the Huntington Study Group found a deterioration of functional capacity of 0.72 units over 1 year, which is equal to a variety of other natural studies. 9,11,12 Moreover, we hereby suggest clustering the motor component of the UHDRS into seven groups for...

Apraxia is the disturbance of planning and of execution of motor activity. It is not caused by a lesion or a disturbance of the motor or sensory nervous system, it is elicited by a dysfunction of an area in the left cortex of the brain. This area in the left fronto-parietotemporal hemisphere is located right beside the area for speech. Therefore it is not unusual that patients with apraxia suffer from aphasia as well. The two different types of limb apraxia are ideomotor apraxia and ideational apraxia. Ideomotor apraxia is apraxia without tool use, it includes imitation of positions of hands and fingers, performance of gestures on demand, and pantomime of object use. Ideational apraxia is apraxia with tool use like cutting with a knife or utilizing a pencil.

Minocycline, the 7-dimethylamino-6-dimethyl-desoxytetracycline hydrochloride, is a caspase-1 inhibitor and may serve as anti-apoptotic agent, thereby acting neuroprotective. It directly inhibits both caspase-independent and -dependent mitochondrial cell death pathways, and decreases inducible nitric oxide synthetase activity. Minocycline delays disease progression in the transgenic mouse model of Huntington's disease (HD), extending survival by 14%. HD is a late onset relentlessly progressive, neurodegenerative disorder with currently no cures or even effective therapies, death occurring 15 years after onset. In this review, recent clinical and preclinical data on minocycline in HD and neuroprotective alternatives discussed.