Association between thermal threshold abnormalities and peripheral artery disease in patients with type 2 diabetes.

Both diabetic peripheral neuropathy and peripheral arterial disease (PAD) cause foot ulcers and often result in non-traumatic amputations in patients with type 2 diabetes. This study aimed to evaluate the association between clinical variables, PAD, and subclinical diabetic small fiber peripheral neuropathy detected by abnormal thermal thresholds of the lower extremities in patients with type 2 diabetes.We investigated 725 consecutive patients with type 2 diabetes (male/female: 372/353; mean age, 67 ±â€Š11 years) who did not have apparent cardiovascular disease (including coronary artery disease, arrhythmia, and stroke) and who underwent the quantitative sensory test for thermal (warm and cold) thresholds of the lower limbs and ankle-brachial index (ABI)/toe-brachial index (TBI) examinations in 2015. The analyses included glycated hemoglobin, estimated glomerular filtration rate, and other characteristics.In total, 539 (74.3%) patients showed an abnormality of at least 1 thermal threshold in their feet. All patients with an abnormal ABI (<0.9) had concurrent impaired thermal thresholds, and 93% (87/94) of patients with an abnormal TBI experienced abnormal thermal thresholds in the lower limbs. Age- and sex-adjusted TBI and estimated glomerular filtration rate were significantly correlated to abnormal thermal thresholds. In the multivariate analysis, fasting plasma glucose, and glycated hemoglobin were independently associated with abnormal thermal thresholds in the lower extremities.Subclinical thermal threshold abnormalities of the feet are significantly associated with PAD and nephropathy in patients who have type 2 diabetes without cardiovascular disease.

Association between the characteristics of metabolic syndrome and Alzheimer's disease.

Various epidemiological studies have shown that type 2 diabetes and metabolic syndrome are highly correlated with Alzheimer's disease (AD). Here, we sought to assess the impact of metabolic syndrome characteristics on the progression of AD. Five-week-old male, spontaneously hypertensive (n = 32) and Wistar Kyoto (abbreviated WKY; n = 8) rats were divided into 5 groups (each n = 8): WKY, hypertension (HTN), streptozotocin-induced diabetes (STZ), high-fat diet (HFD), and STZ + high-fat diet-induced diabetes mellitus (DM). All animals were sacrificed and samples of the blood, liver, and brain were collected for further biological analysis. During the 15-week period of induction, the STZ and DM groups (animals injected with low-dose STZ) had significantly higher fasting glucose levels; the HFD group had elevated insulin levels, but normal blood glucose levels. The HFD and DM groups had hypercholesterolemia and higher hepatic levels of triglycerides and cholesterol. Additionally, correlations between HFD and elevated brain amyloid-beta 42 (Aß-42), hyperglycemia and down-regulation of brain insulin receptor, and serum Aß-42 and hepatic triglyceride concentrations (r(2) = 0.41, p < 0.05) were observed. Serum C-reactive protein and malondialdehyde did not appear to have a significant influence on the association with biomarkers of AD. Thus, our study demonstrated that rats with characteristics of metabolic syndrome had a large number of biomarkers predicting AD; however, no relationship between traditional inflammatory and oxidative markers and AD was found. Further studies are necessary to prove that these findings in rats are relevant to AD processes in humans.

Preserved motor-evoked potentials but without good motor recovery in a patient with decerebrate rigidity.

The corticospinal tract is not incriminated in decerebrate rigidity (DR). However, this has not yet been proven in humans. We applied transcranial magnetic stimulation (TMS) in a decerebrate patient to support the hypothesis. A patient suffering from pontine hemorrhage with the fourth ventricular extension was admitted unconscious and in a decerebrate posture. Five days later, she regained consciousness but remained in a decerebrate posture. Motor-evoked potentials (MEPs) to TMS were measured 1 week after she had regained consciousness, and this provoked muscle responses in her hands and feet bilaterally. During the follow-up, the patient's muscle tone became persistently flaccid, although her strength increased to varying degrees in different body and limb muscles. She remained bedridden for 3 years after the stroke and could neither turn on the bed by herself nor perform skilled movements using her hands. The findings of TMS confirmed the animal studies in that the mechanism of decerebrate rigidity did not come through a damage of the corticospinal pathway. This also implies that a preserved corticospinal tract function cannot guarantee a good motor recovery in a stroke patient.

Fatigue as the only clinical manifestation of colchicine induced myopathy.

PURPOSE: Fatigue may be induced by drug. Here, we reported that patients had fatigue after medication with colchicines. METHOD: Eight patients (8 Males, age: 42-72 years old) had fatigue but without weakness as their chief complaints. They all described an inability to maintain a sustained effort, which was ameliorated by rest. RESULTS: The course of fatigue was insidious and progressive (mean 3.1 2.3 months, range 1-7 months) along with medication of colchicines (mean 20.3 5.5 months, range 11-28 months). Fatigue severity scale (patient: before drug withdrawal 5.41 0.19; 4 weeks after drug withdrawal 2.46 0.28; control 2.12 0.45) showed fatigue as their most disabling symptom, sometimes preventing them to carry on professional as well as socio-familial activities. The plasma creatine kinase elevated in these 8 patients before withdrawal of colchicines and returned to normal range in each subject 4 weeks after drug withdrawal. A probable diagnosis of drug-induced fatigue was made when symptom subsided after colchicines were discontinued. CONCLUSION: It is emphasized that side effect of drug should be considered as a differential diagnosis of fatigue in patients having colchicines. Early recognition and diagnosis will prevent serious muscle damage.

A flow chart proposed for early diagnosis of cryptococcal infection as a cause of stroke.

An 82-year-old woman had a transient ischemic attack and stroke of the left middle cerebral artery syndrome that turned out to be attributed to cryptococcal meningoencephalitis (CM). An initial presentation of central nervous system infection, such as fever and headache, was absent. It was masked by chronic use of corticosteroids and immunosuppressants for her rheumatoid arthritis. The diagnosis was made by the clinical setting of stroke-in-evolution and progression of hydrocephalus on the second brain imaging study. In this case, we discuss the atypical presentation of CM in an immunosuppressed patient and offer a flow chart for early diagnosis, thus improving outcome and survival rates.

Gabapentin for decerebrate rigidity: a case report.

A 48-year-old woman suddenly lost consciousness as a result of a right rostral pontine tegmentum haemorrhage. The patient presented with decerebrate rigidity (DR) and regained full consciousness 5 days after the initial onset. The patient was given gabapentin 1200 mg/day nasogastrically and her DR significantly improved, although other antiepileptic drugs such as phenytoin and carbamazepine were given in larger dosages to decrease muscle hypertonicity. The patients' preserved consciousness and motor-evoked potentials to transcranial magnetic stimulation indicated a derangement of the extrapyramidal tracts with preservation of the pyramidal tracts. This case report discusses the possible mechanisms of action of gabapentin in DR.

Brainstem excitability is increased in subjects with palmomental reflex.

BACKGROUND/PURPOSE: The palmomental reflex (PMR) is a brief contraction of the mentalis muscles caused by a scratch over the thenar eminence, i.e. a brainstem reflex to afferents of upper limb. Using electrophysiologic methods, we studied the characteristics of brainstem excitability in PMR subjects. METHODS: Ten healthy PMR subjects were included in the study. Brainstem excitability was assessed with electrical stimulation at the trigeminal nerve, median nerve, ulnar nerve, and sural nerve with recordings at the mentalis muscles. A comparison was made by the probability between the mechanical scratch and the electrical stimulation to evoke the visible muscle contraction of mentalis. RESULTS: An electrical stimulus was able to elicit mentalis muscle responses (MMR(electrical)) in all the subjects if the stimulus was of sufficient strength. Using electrical stimulation, the median nerve at the wrist was the best site to evoke MMR(electrical). However, in PMR subjects, the probability of MMR(electrical) to median nerve stimulation was less than that of MMR(scratch), i.e. the clinical findings of PMR. Significantly lower thresholds and higher amplitudes were noted in PMR subjects only when the median nerve was stimulated. The onset latency did not show any difference between the two groups despite the stimulation sites. CONCLUSION: The facial motor neurons to median nerve stimulation are more sensitive in PMR subjects. In healthy PMR subjects, this indicates that the excitability increases only in the specific neuronal circuits between the lower cervical spinal cord and the facial motor nucleus in the rostral medulla. MMR(electrical) is a physiologic phenomenon, and PMR is a sign of increased brainstem excitability.

Mentalis muscle responses to median nerve stimulation.

Electrical stimulation may produce excitation or inhibition of the motor neurons, as represented the blink reflex and masseter silent period in response to trigeminal nerve stimulation. Clinically, a light touch on the palm may evoke a mentalis muscle response (MMR), i.e. a palmomental reflex. In this study, we attempted to characterize the MMR to median nerve stimulation. Electrical stimulation was applied at the median nerve with recordings at the mentalis muscles. An inhibition study was done with continuous stimuli during muscle contraction (I1 and I2 of MMRaverage). Excitation was done with a single shot during muscle relaxation (MMRsingle) or by continuous stimuli during muscle contraction (E1 and E2 of MMRaverage). The characteristic differences between MMRaverage and MMRsingle were as follows: earlier onset latencies of MMRaverage (MMRaverage < 45 ms; MMRsingle > 60 ms), and a lower amplitude of MMRaverage (MMRaverage < 50 microV; MMRsingle > 150 microV). The receptive field of MMRsingle was widespread over the body surface and that of MMRaverage was limited to the trigeminal, median and index digital nerves. Series of stimuli usually significantly decreased the amplitude of MMRsingle, as a phenomenon of habituation. On the other hand, it was difficult to evoke the earlier response (i.e. MMRaverage) without continuous stimuli and an average technique. MMRaverage had the components of both excitation (E) and inhibition (I); for example, E1-I1-E2-I2 or I1-E2-I2. E2 was the most consistent component. In patients with dorsal column dysfunction, median nerve stimulation could successfully elicit MMRsingle, but not MMRaverage. Contrarily, in patients with pain sensory loss, it was more difficult to reproduce MMRsingle than MMRaverage. It seemed that MMRaverage and MMRsingle did not have equivalents across the different modalities of stimulation.

Hydrocephalus associated with Guillain-Barre syndrome.

A 68-year-old man developed progressive four-limb weakness and areflexia 17 days after an influenza vaccination. He was diagnosed with Guillain-Barre syndrome (GBS), and remained ventilator dependent and bed-bound for 3 months, despite plasmapheresis and immunoglobulin infusion. However, cognitive impairment, excessive daytime sleepiness, and motor disability were still present, even when he was no longer ventilator dependent. Brain computerized tomography scan and isotope cisternography was consistent with normal pressure hydrocephalus. His motor control and cognitive function recovered almost completely after insertion of a ventriculoperitoneal shunt. Although hydrocephalus is not frequently associated with GBS, our case report indicates that brain imaging is necessary in GBS patients whose cognitive functions deteriorates after disease onset.

Transcranial magnetic stimulation in patients with transient ischemic attacks.

BACKGROUND: By definition, transient ischemic attacks (TIAs) do not leave a neurological deficit beyond 24 hours after onset. However, a subgroup of TIA patients is characterized by persistent perfusion defect on single photon emission computed tomogram or infarction on brain computerized tomogram and magnetic resonance imaging. Here, we applied transcranial magnetic stimulation (TMS) to study whether TIA could produce persistent subclinical dysfunction for more than 24 hours. METHODS: The study included 23 TIA patients who had the criteria of hand weakness as one of their clinical manifestations. TMS was done twice in each TIA patient. The first time was during the period of 24-48 hours after onset and the second 7 days after onset. We studied the cortical motor threshold, the latencies and the amplitudes of the motor evoked potentials, the central motor conduction time, and the cortical silent period at the intensity of 1.5 times motor threshold with maximal voluntary isometric contraction. The recording was at the first dorsal interosseous muscle. RESULTS: There was no significant difference between the whole group of TIA patients and normal control. However, in the subgroup of TIA patients who had hand weakness more than 1 hour, they had increased motor threshold and prolonged cortical silent period during the first test. Both improved 1 week after onset. On the contrary, in TIA patients who had hand weakness less than 1 hour, their data were all within normal limits during the first and the second studies. CONCLUSIONS: Our results indicate that the motor function of TMS study will recover to full if the motor symptoms subside within 1 hour in TIA patients. Subclinical motor deficits may persist in TIA patients who have motor symptoms more than 1 hour.

Hypotension due to interaction between lisinopril and tizanidine.

OBJECTIVE: To report a case in which significant hypotension occurred after initiation of tizanidine in a patient using the antihypertensive agent lisinopril. CASE SUMMARY: A 48-year-old woman was admitted due to cerebral hemorrhage at the midbrain and pons, with extension to the fourth ventricle. Consciousness disturbance (Glasgow coma scale 4) with a decerebrate posture improved 5 days after stroke onset. As the BP was fairly high, antihypertensive agents, including lisinopril, were initiated. Three weeks later, the decerebrate rigidity and high BP remained, and tizanidine was initiated to see whether the decrease in muscle tone could facilitate hypertension control and motor recovery. However, the BP dropped dramatically within 2 hours after the first dose of tizanidine. The tizanidine and all of the antihypertensive medications were withdrawn. Tizanidine was used again after her BP had stabilized, but did not produce similar problems. DISCUSSION: A similar event was reported in 2000. The reaction in our patient appeared after tizanidine initiation and improved after both lisinopril and tizanidine were discontinued. According to the Naranjo probability scale, this was classified as a possible drug interaction. This kind of reaction is seldom mentioned as occurring during co-administration with tizanidine. With its characteristics, tizanidine has the potential to compromise hemodynamic stability during concomitant angiotensin-converting enzyme inhibitor use. CONCLUSIONS: Based upon the literature review, the hypotension in this patient was possibly due to the interaction between tizanidine and lisinopril.

Subtle brain dysfunction in treated 6-pyruvoyl-tetrahydropterin synthase deficiency: relationship to motor tasks and neurophysiological tests.

6-Pyruvoyl-tetrahydropterin synthase (6PTPS) deficiency is a major cause of biopterin deficiency. 6PTPS patients usually have an elevated serum phenylalanine level, a deficiency of neurotransmitters (serotonin and dopamine), and neurological symptoms, if without treatment. We herein investigated the possibility of neurological dysfunction in early-treated patients. In the study, 12 early-treated 6PTPS patients were studied. Their auditory simple reaction time, movement rhythm variation (MRV), somatosensory evoked potentials to median nerve stimulation, and hand muscle responses to transcranial magnetic stimulation, were measured. MRV is a test of repetitive voluntary movements, and was used with and without auditory cues at 0.3 Hz. The 6PTPS patients had an increased motor threshold but normal motor and sensory central conduction times. They performed very well in simple reactions (6PTPS 208.4+/-16.7 ms, control 200.3+/-11.7 ms, p=0.18), but not in continuous tasks. The continuous performance tests showed that MRV had increased in the 6PTPS patients (with cues: 6PTPS 7.35+/-0.94, control 5.47+/-0.80, p<0.0001; without cues: 6PTPS 9.87+/-1.44, control 6.59+/-0.68, p<0.0001). Without cues, MRV had increased in both the 6PTPS and control groups, but more significantly in the 6PTPS patients (6PTPS 2.51+/-0.97, control 1.25+/-0.42; p=0.0001). Our findings indicate that early-treated 6PTPS patients have subtle neurological dysfunctions. They may not maintain movement rhythm as well as normal subjects, even with external cues. Hence, MRV is a good method to assess motor control.

Guillain-Barré syndrome coexisting with pericarditis or nephrotic syndrome after influenza vaccination.

A 68-year-old woman and a 72-year-old man presented with distal weakness of the limbs and numbness following an influenza vaccination within 2 weeks. Moreover, Guillain-Barré syndrome (GBS) was diagnosed in two patients. Pericarditis was diagnosed in the first patient who also had precordial chest pain with referral to trapezius ridge, and nephrotic syndrome, was observed in the second patient who had leg edema and proteinuria. The relationship among GBS, pericarditis and nephrotic syndrome after an influenza vaccination is discussed.

Differential effects of stimulus intensity on peripheral and neuromagnetic cortical responses to median nerve stimulation.

To study the differential effects of tactile stimulus intensity on cortical and peripheral responses, we measured neuromagnetic cortical responses, compound muscle action potentials (CMAP), sensory nerve action potentials (SNAP), and the subjective estimation of tactile magnitude to electric median nerve stimulation at the wrist in 13 male healthy adults. The sensory perception threshold (ST) for electric pulses at wrist skin was determined and then various levels of stimulus intensity (1 approximately 6 ST) were given to each subject. At 1 ST, only the P50m components of the primary somatosensory (SI) cortical responses were recorded. The second somatosensory (SII) cortical responses were saturated at 2 ST, while the SI responses reached maximum at 3 ST equivalent to the subjective threshold intensity for "strong" tactility. The CMAP and SNAP were maximum at 4-5 ST. At 2 ST, >70% of maximum SI responses were produced, whereas only <40% of maximum CMAP or SNAP responses were obtained. We concluded that the stimulus intensities for activating or saturating somatosensory cortical responses were lower than those for CMAP and SNAP. The differential intensity effects on cortical and peripheral responses suggest a polysynaptic organization underlying the central amplification for somatosensory cortical activation. The optimal intensity levels for producing maximum SI and SII responses were 3 and 2 ST, respectively. Compared with the SII, the SI plays a crucial role in the coding of the tactile stimulus intensity.

Using electrodiagnostic machine to study movement rhythm variation.

BACKGROUND: Hand movement constitutes the most common daily activities in our life. Hand dexterity is often impaired in patients with neurological disease. We developed an adjunct method, based upon the electrodiagnostic software, for study of motor control and hand dexterity. METHODS: Thirty-two normal subjects, 2 stroke patients and 2 Parkinson patients were included in the study. All of them were right-handed, and were asked to pace rhythmic finger tapping at a comfortable rate without cue or any external stimuli. A trigger kit was designed to transform the finger tapping. After using the triggering mode and adjusting the sweep speed, 2 tapping signals were simultaneously displayed on the screen. The first signal was the triggering potential, and the variation in timing of the second signal represented the variation in timing of the inter-response interval. Twenty sweeps were recorded, superimposed and measured on the screen. Movement rhythm variation (MRV) was defined as b/a x 100 (b = [maximal interval of finger tapping - minimal interval of finger tapping]; a = [maximal interval of finger tapping + minimal interval of finger tapping]/2). Each subject started with right hand and then left hand. RESULTS: MRV measurement showed excellent intrarater (r = 0.97) and interrater (r = 0.97) reliability. In normal right-handed subjects, the MRV was better in right hand than in left hand (right 16.5 +/- 4.1% and left 21.0 +/- 7.6%; p < 0.05). The MRV improved in stroke patients along with the recovery and improved in Parkinson patients after levodopa treatment. CONCLUSIONS: MRV was a good method to provide quantitative data for assessment of hand dexterity. Our study also showed the potential role of MRV in motor control study.