[Comorbidity in migraine].

Migraine is a common and often disabling disease with a prominent genetic basis. There are many comorbidities associated with migraine which have been identified as risk factors for progression to chronic migraine. Each of these has its own genetic load and shares some common characteristics with migraine. The identification of migraine comorbidities may help clarify common underlying genetic and biological mechanisms of diseases. The treatment of migraine should involve a multifaceted approach, aimed at identifying and reducing possible risk and comorbidity factors. This may prevent the evolution toward a chronic form and then toward pharmacological resistance.

Clinical correlates of anhedonia in patients with Parkinson's disease.

OBJECTIVE: To investigate the prevalence and clinical correlates of anhedonia in patients with Parkinson's disease (PD) and to also examine the relationship between anhedonia and the QOL. METHODS: One hundred and seventeen patients with PD completed the Snaith-Hamilton Pleasure Scale (SHAPS), the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory Second Edition (BDI-II), Starkstein's Apathy Scale (AS) and a quality of life (QOL) battery. Hoehn and Yahr (HY) staging, the Unified Parkinson's Disease Rating Scale (UPDRS) and the Mini-Mental State Examination (MMSE) were administered on the same day. RESULTS: Anhedonia (SHAPS score≥3) was diagnosed in 15% of the patients. The SHAPS score was found to be significantly correlated with the HY stage and the UPDRS (I, IVB, IVC, total), BDI-II, AS and STAI (State, Trait) scores. A multivariate analysis revealed that the BDI-II and STAI (Trait) scores significantly influenced the SHAPS scores. The SHAPS scores were found to be negatively correlated with the QOL. CONCLUSIONS: These findings indicate that anhedonia is associated with depression and anxiety. In addition, recognizing anhedonia in patients with PD is important since it may have a negative effect on the QOL.

Anxiety and depression in patients with Parkinson's disease.

OBJECTIVE: To investigate the prevalence and clinical correlates of anxiety and depression in patients with Parkinson's disease (PD) and to examine the relationship between anxiety and depression and the quality of life (QOL). METHODS: One hundred and seventeen patients with PD completed the state-trait anxiety inventory (STAI), the beck depression inventory second edition (BDI-II), Starkstein's apathy scale (AS) and QOL battery. Hoehn and Yahr (HY) staging, the unified Parkinson's disease rating scale (UPDRS) and the mini-mental state examination (MMSE) were administered on the same day. RESULTS: Anxiety (STAI score ≥41 for men or ≥42 for women) was diagnosed in 55% of the patients and depression (BDI-II score ≥14) was diagnosed in 56% of the patients. Anxiety coexisted with depression in 41% of the patients, while depression without anxiety was observed in 15% of the patients and anxiety without depression was observed in 14% of the patients. The STAI score was found to be significantly correlated with the UPDRS (I, IV) and AS scores, whereas the BDI-II score was found to correlate with the HY stage and the UPDRS (I, III, IV) and AS scores. Both the STAI and BDI-II scores were found to negatively correlate with QOL. A multivariate analysis revealed that depression and anxiety are similarly associated with the PD specific QOL (PDQ-39), while motor severity, as judged by the HY stage and UPDRS III score, is not. CONCLUSION: These findings indicate that recognizing anxiety and depression in patients with PD is important, since both conditions are commonly observed in patients with PD and are similarly associated with the QOL, independent of motor severity.

Three cases of nummular headache effectively treated with Neurotropin(®).

We herein present three consecutive cases of nummular headache treated with Neurotropin (NTP). Case 1: A 71-year-old man developed a headache in a circumscribed area of the left parietal region. Treatment with NTP resolved the pain after three months. Case 2: A 57-year-old woman developed bifocal pain in both temporal regions. NTP therapy slightly relieved the pain, although the headache remained. Case 3: A 39-year-old man developed bifocal pain the left temporal region. Treatment with NTP resolved the pain after five days. The present results suggest that NTP may be effective for treating patients with nummular headaches.

[Cognitive impairment in Parkinson's disease].

Cognitive impairment is a common finding in Parkinson's disease (PD), even in the early stages. The concept of mild cognitive impairment (MCI) in PD was recently formalized with diagnosis being reached after impairments in neuropsychological tasks become significant in at least one domain. The brain profile of cognitive deficits involves executive functions (e. g., planning, set shifting, set maintenance, problem solving), attention and memory function. Memory deficits are characterized by impairments in delayed recall, temporal ordering and conditional associate learning. PD patients demonstrate relatively preserved recognition. Visuospatial dysfunctions have also been reported, while language is largely preserved. The existence of two distinct mild cognitive syndromes has also been suggested. One of these affects mainly the frontostriatal executive deficits that are modulated by dopaminergic medications and by a genetically determined level of prefrontal cortex dopamine release. The other affects the more-posterior cortical abilities, such as visuospatial and memory functions, and is suggested to be associated with an increased risk for conversion to dementia. Cross-sectional studies have commonly reported dementia in 20-30% of PD patients, although the 8-year cumulative incidence of dementia may be as high as 78%. Factors associated with dementia in PD are age at onset, age at the time of examination, akinetic-rigid form PD, depression, hallucination, rapid eye movement sleep behavioral disorder and severe olfactory deficits. Clinical features generally involve the same type of deficits as those found in MCI patients, which are more severe and more extensive. The phenomenology of the dementia syndrome is similar to that seen in dementia with Lewy bodies, and clinicopathological correlation studies have revealed varying results with regard to neurochemical deficits and the pathological substrate underlying cognitive impairment and dementia. Early cognitive impairment, particularly in the form of executive dysfunction, is indicative of mainly fronto-striatal pathologic changes and might originate during nigrostriatal and subsequent mesocortical dopamine denervation. A potential parallel noradrenergic deficit and cholinergic deficit disturbance in patients without dementia might also contribute to MCI. Extensive pathological changes in Lewy bodies lead to widespread cortical and subcortical degeneration and profound cholinergic deficits, and might lead to the development of dementia. Several studies have revealed a significant correlation between dementia and Alzheimer-type pathology.

Clinical features of 16 cases of headache which were provoked after watching 3-D videos.

OBJECTIVE: Although a lot of people have recently reported headaches provoked after watching 3-D videos, the clinical features of the so-called "3-D headache" have not been clarified. In this study, we investigated the clinical features of headaches provoked after watching 3-D videos. METHODS: We conducted a questionnaire survey by email to cases who described headaches caused by watching 3-D videos on a Weblog. We established the diagnostic criteria for 3-D headaches, which are as follows for a definite 3-D headache: A) Provoked after watching 3-D videos, but was never provoked by 2-D videos, B) Never experienced previously, C) Unclassifiable by the ICHD-II. A possible 3-D headache was one that met the criteria of A) and B) the same as above, C) Classified as a "probable" subform by the International Classification of Headache Disorders-2nd Edition (ICHD-II). RESULTS: We received answers from 16 cases (5 males, 11 females, average age of 35.8 years old). Eleven of the 16 cases had experienced an entirely new type of headache after watching 3-D videos. Of these 11 cases, 5 were diagnosed as having a definite "3-D headache". The other 6 cases were diagnosed as having possible 3-D headaches. The remaining 5 of 16 cases were suspected to be attacks of primary headaches that the cases were accustomed to having experienced. The common characteristics of the 5 definite 3-D headaches were that they were bilateral and non-pulsating, and the duration was from 10 minutes to 24 hours. The intensity of the 3-D headache was as follows; severe in 2 cases, moderate in 2 cases, and mild is one case. Three of the 4 cases with moderate to severe headache had nausea. CONCLUSION: The headaches provoked after watching 3-D videos include not only the attacks of primary headaches but also the headache attacks unclassifiable by the ICHD-II.

Factors associated with functional outcomes of patients with cerebral embolism due to nonvalvular atrial fibrillation.

OBJECTIVE: This study aimed to identify factors associated with the functional outcomes of patients with cerebral embolism due to nonvalvular atrial fibrillation. METHODS: We retrospectively investigated the short-term functional outcomes of 134 patients diagnosed with cardiogenic cerebral embolism due to nonvalvular atrial fibrillation during the period of May 2006 to August 2008. Functional state was evaluated using the modified Rankin Scale (mRS) on admission and at discharge. RESULTS: A good functional outcome (mRS ≤2) at discharge was significantly associated with low mRS on admission (OR: 0.07; CI: 0.03-0.18; p<0.001), and a low C-reactive protein (CRP) level (OR: 0.19; CI: 0.04-0.89; p<0.05). Functional improvement during admission was positively associated with the presence of dyslipidemia (OR: 2.74; CI: 1.11-6.76; p<0.05), whereas high diastolic blood pressure (OR: 0.95; CI: 0.90-0.99; p<0.05) and a high blood sugar level (OR: 0.98; CI: 0.97-0.99; p<0.05) on admission were inversely associated with functional improvement. Furthermore, no relationship existed between mRS on admission and functional improvement during hospitalization. CONCLUSION: The results suggest that a good functional state at discharge was associated with a good functional state on admission as well as a low serum CRP level. On the other hand, functional improvement was associated with the presence of dyslipidemia, low diastolic blood pressure, and low blood sugar level on admission.

Apathy and depression in Parkinson disease.

The purpose of this study was to investigate the prevalence and clinical correlates of apathy and depression in Parkinson disease (PD), and to clarify whether apathy can be dissociated from depression. One hundred fifty patients with PD completed the Beck Depression Inventory Second Edition (BDI-II), Starkstein's Apathy Scale (AS), and a quality of life (QOL) battery. Hoehn and Yahr (HY) staging, the Unified Parkinson's Disease Rating Scale (UPDRS), and the Mini-Mental State Examination (MMSE) were performed on the same day. Apathy (AS score > or = 16) was diagnosed in 60% of patients and depression (BDI-II score > or = 14) in 56%. Apathy coexisted with depression in 43% of patients, compared with depression without apathy in 13% and apathy without depression in 17%. Apathy scale score was significantly correlated with UPDRS scores, HY stage, and age, whereas BDI-II score was correlated only with UPDRS scores. Both AS and BDI-II scores were negatively correlated with QOL. However, multiple regression analysis revealed that depression was strongly and negatively associated with emotional well-being and communication, whereas apathy was mainly associated with cognition and stigma. These findings suggest that apathy and depression may be separable in PD, although both are common in patients with PD and are associated with QOL.

Primitive reflexes distinguish vascular parkinsonism from Parkinson's disease.

OBJECTIVES: Although vascular parkinsonism (VP) occurs frequently in the elderly, its clinical features have not been investigated in detail, particularly in comparison with Parkinson's disease (PD). The goal of this study is to clarify the diagnostic value of pathological reflexes in differentiating between VP and PD. PATIENTS AND METHODS: In 132 patients with PD and 55 with VP, pathological reflexes, including snout reflex (SR), palmomental reflex (PMR), corneomandibular reflex (CMR), jaw reflex (JR), Hoffmann reflex (HR), and extensor plantar response (EPR), were evaluated. RESULTS: The percentage of each pathological reflex elicited in two groups (VP:PD) was as follows: SR (78:30), PMR (53:26), CMR (9:6), JR (33:12), HR (29:11), and EPR (25:8). The prevalence of pathological reflexes, except for CMR, was significantly higher in the VP patients than in the PD patients. In particular, SR and PMR were more frequent than upper motor neuron signs in the VP patients. The sensitivity and specificity of either SR or PMR for VP were 84% and 82%. CONCLUSION: Snout and palmomental reflexes are useful tools in the differentiation between VP and PD.

Recognition memory for unfamiliar faces in Parkinson's disease: behavioral and electrophysiologic measures.

We analyzed event-related potentials (ERPs) and behavioral measurements during a recognition memory task in 15 normal elderly subjects and 15 patients with Parkinson's disease (PD). To elicit ERPs unfamiliar faces were repeated immediately after initial presentation (at lag 0), after one intervening face (at lag 1) or at lag 3. Compared to normal controls, PD patients showed decreased accuracy in recognizing new unfamiliar faces. P170 latency and amplitude were similar between both groups. ERP amplitude between 300 and 500 ms after the stimulus in control subjects showed a positive shift (ERP repetition effect) for lag 0 at all sites and for lag 1 and 3 repetitions at the Fz site, while effects in the PD group were not noted at any site, even for the lag 0 repetition. ERP waveforms for the first presentation of faces in PD patients showed a significant positive shift compared to normal controls. These data suggest intact perception but impaired recognition memory for unfamiliar faces in PD. In addition, recognition memory deficits in PD may result from impairment of comparison of structural representations of presented faces with stored representations of faces known to the observer.

Four mutations of the spastin gene in Japanese families with spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.

Cerebral blood flow in Parkinson's disease, dementia with Lewy bodies, and Alzheimer's disease according to three-dimensional stereotactic surface projection imaging.

Regional brain perfusion was analyzed using single-photon emission computed tomography with three-dimensional stereotactic surface projections (3D-SSP) in 69 patients with Parkinson's disease (PD), 16 patients with dementia with Lewy bodies (DLB) and 15 patients with Alzheimer's disease (AD), and compared with that in 24 age-equivalent normal subjects. Nondemented PD patients revealed less parietal and frontal flow than controls. With mental impairment, flow reduction extended to other areas including occipital regions. PD with dementia and DLB showed similar reduction patterns, although frontal flow showed a greater reduction in DLB. AD showed little occipital reduction, but a severe parieto-temporal reduction. Thus, 3D-SSP appears to be useful in the detection of cortical lesions and the differential diagnosis of patients with cognitive impairment.

Oct6, a transcription factor controlling myelination, is a marker for active nerve regeneration in peripheral neuropathies.

Three transcription factors, Krox20 (EGR2), Oct6 (SCIP/Tst1) and Sox10, are considered necessary for transition from the nonmyelinating to the myelinating stage of Schwann cell development. We immunohistochemically studied Oct6 expression in peripheral nerve specimens from 25 patients with various diseases including Charcot-Marie-Tooth disease type 1A (CMT1A). Oct6 was present in cytoplasm of Schwann cells associated with normal-appearing myelinated nerve fibers, but not in nuclei. Expression was seen in nuclei of Schwann cells in the early phase of acute axonal degeneration; nuclear expression peaked at the regenerative stage. Schwann cells forming "onion bulbs" expressed Oct6 in chronic inflammatory demyelinating polyneuropathy (CIDP), but showed minimal expression in CMT1A, reflecting their proliferative activity in CIDP. Nerves showing chronic axonal loss had no expression. Oct6, then, may be a marker for dedifferentiation of adult Schwann cells and active nerve regeneration.

[A case of motor neuron disease with dementia and apraxia of the upper limbs].

We report a 61-year-old, right-handed woman with motor neuron disease, dementia, and apraxia of the upper limbs. The patient developed clumsiness of the right hand and dysarthria two years and a half prior to admission. Neurological examination showed limb-kinetic apraxia and ideomotor apraxia, predominantly on the right side, in addition to dementia and anarthria. There was mild muscle wasting in the neck and hands. A muscle biopsy from the biceps muscle of arm as well as needle EMG revealed neurogenic changes compatible with motor neuron disease. Brain MRI indicated pyramidal tract degeneration. Three-dimensional brain perfusion imaging generated from SPECT demonstrated an asymmetric decrease in cerebral blood flow in the fronto-temporo-parietal regions, predominantly on the left side. This case suggests that asymmetric limb apraxia can be associated with motor neuron disease.