Measurement of excitation-contraction coupling time in critical illness myopathy.

OBJECTIVE: This study aimed to develop a simple and reliable technique to assess excitation-contraction (E-C) coupling for early diagnosis of critical illness myopathy (CIM). METHODS: We prospectively performed clinical and electrophysiological examinations on patients admitted to intensive care unit (ICU). In addition to full neurological examinations and routine nerve conduction study, motor related potential (MRP) was recorded using an accelerometer attached to the base of hallux after tibial nerve stimulation, and E-C coupling time (ECCT) was measured from the latency difference between soleus compound muscle action potential (CMAP) and MRP. RESULTS: Of 41 patients evaluated, 25 met the criteria for ICU-acquired weakness, 23 of whom had CIM. The time to the first electrophysiological examination (time to first test) correlated negatively with CMAP and with MRP. Conversely, a positive correlation was observed between the time to first test and ECCT. E-C coupling impairment occurred in most of our patients with CIM by the third day of ICU admission, and prolonged ECCT could be the earliest detectable abnormality. CONCLUSIONS: The ECCT measurement is an easy and reliable technique to detect reduced muscle membrane excitability in the early stage of CIM. SIGNIFICANCE: The ECCT measured by our method using an accelerometer may be a parameter that predicts the development of CIM.

Effect of local cooling on excitation-contraction coupling in myasthenic muscle: Another mechanism of ice-pack test in myasthenia gravis.

OBJECTIVE: The ice-pack test is a convenient diagnostic testing procedure for myasthenia gravis (MG). We investigated the underlying mechanism of the ice-pack test performed on bilateral masseters. METHODS: We performed trigeminal repetitive nerve stimulation (RNS), excitation-contraction (E-C) coupling assessment (Imai's method) and bite force measurement before and after cooling of the masseters in MG patients and normal controls. After placing the ice-pack on the masseters for 3min, serial recordings of the three tests were performed at various time intervals during 10min after cooling. RESULTS: The bite force increased significantly after cooling in ice-pack-positive MG patients. The acceleration and acceleration ratio (acceleration at a given time to baseline acceleration) of jaw movement increased significantly after cooling of the masseters in ice-pack-positive MG patients compared to ice-pack-negative patients and normal controls. The prolonged effect of cooling continued until the end of recording even though decremental response to RNS had returned to baseline value. CONCLUSIONS: Cooling of myasthenic muscle may induce two effects. One is relatively short effect on electrical synaptic transmission at the endplate, and another is prolonged effect on E-C coupling in the muscle. SIGNIFICANCE: The ice-pack test induces a prolonged effect of ameliorating impaired E-C coupling in MG.

Impaired post-tetanic potentiation of muscle twitch in myasthenia gravis.

OBJECTIVE: The aim of this study was to evaluate post-tetanic potentiation of muscle twitch in myasthenia gravis (MG). METHODS: Post-tetanic potentiation was evaluated by recording the compound muscle action potential (CMAP) of abductor pollicis brevis and movement-related potential (MRP) of the thumb using an accelerometer after tetanic stimulation of the median nerve at the wrist. After baseline recording, tetanic stimulation was delivered to the median nerve at a frequency of 10 Hz for 10s. The CMAP and MRP were successively recorded at baseline and at 5, 10, 30, 60, 90 and 120 s after tetanic stimulation. The chronological changes of CMAPs and MRPs were recorded bilaterally in 11 patients with MG, 9 patients with myopathies (disease controls), and 25 healthy control subjects. RESULTS: Maximal acceleration of MRP was significantly elevated during 10s after tetanic stimulation without any CMAP changes in all groups. However, statistical analysis detected a significant decrease in post-tetanic potentiation of maximal acceleration of MRP in MG patients only compared to healthy controls, but not in myopathy patients, which may imply impairment of excitation-contraction coupling in MG. CONCLUSIONS: Post-tetanic potentiation of muscle twitch is significantly diminished in MG, suggesting impaired excitation-contraction coupling. SIGNIFICANCE: Measurement of post-tetanic potentiation using an accelerometer is a simple and sensitive method to detect impairment of excitation-contraction coupling in MG.

Respiratory insufficiency with preserved diaphragmatic function in amyotrophic lateral sclerosis.

OBJECTIVE: We performed a longitudinal study to elucidate the correlation between respiratory insufficiency and respiratory biomarkers, including diaphragmatic compound muscle action potential (DCMAP), at the initiation of noninvasive ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). METHODS: The patients were assessed at least every six months. Additional assessments were performed at the start of respiratory therapy when the patients met the criteria for the initiation of NIV. Each assessment consisted of a full neurological examination, a phrenic nerve conduction study, respiratory function tests, and nocturnal pulsed oximetry. PATIENTS: We enrolled 43 patients with either definite or probable ALS as defined by the revised El Escorial criteria. RESULTS: The patients were divided into two groups according to the timing of the initiation of respiratory therapy. Seventeen patients (group A) met the criteria for NIV initiation when their DCMAP remained normal. Twenty-six patients (group B) met the criteria when their DCMAP decreased below normal limits. Although respiratory function parameters were significantly worse in group B compared with group A at NIV initiation, more than 80% of the patients in both groups developed nocturnal desaturation during sleep. CONCLUSION: DCMAP is not always a reliable indicator for determining the optimal timing for NIV initiation during the progression of respiratory insufficiency in ALS. Physicians should be aware of the risk of respiratory insufficiency during sleep in patients with ALS.

Early effect of tacrolimus in improving excitation-contraction coupling in myasthenia gravis.

OBJECTIVES: Tacrolimus (FK506) is a macrolide T-cell immunomodulator used to treat myasthenia gravis (MG). Besides immunosuppression, tacrolimus has been reported to have the potential to increase muscle strength by enhancing ryanodine receptor (RyR) function. However, few attempts have been made to demonstrate the early effect of tacrolimus as an RyR enhancer in clinical investigation. METHODS: In 20 MG patients, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The excitation-contraction (E-C) coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT and bite force were performed before and within 4 weeks of tacrolimus (3 mg day(-1)) treatment. The median (mean, range) interval of assessment was 2 (2.4, 1-4) weeks. We also measured serum antibodies against RyR, acetylcholine receptor and muscle-specific receptor tyrosine kinase. RESULTS: Bite force increased after tacrolimus treatment accompanying clinical improvement assessed by Myasthenia Gravis Foundation of America classification, but the bite force difference did not reach statistical significance. Wilcoxon matched-pairs signed-ranks test detected a significant ECCT shortening in 12 patients assessed after 1-2 weeks of tacrolimus treatment as well as in eight patients assessed after 3-4 weeks. In contrast, masseteric CMAP and % decrement showed no significant changes after short-term tacrolimus treatment. CONCLUSIONS: Tacrolimus induces ECCT shortening accompanying clinical improvement despite no improvement in % decrement within 2 weeks. SIGNIFICANCE: This early effect of tacrolimus may imply a pharmacological enhancement of RyR function to improve E-C coupling in MG.

Contribution of anti-ryanodine receptor antibody to impairment of excitation-contraction coupling in myasthenia gravis.

OBJECTIVE: The aim of this study was to elucidate the relationship between the impairment of excitation-contraction (E-C) coupling and anti-ryanodine receptor (RyR) antibody in patients with myasthenia gravis (MG). METHODS: Masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRPs) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated as the latency difference between CMAP and MRP. For each patient, we selected a representative data set when there was no abnormal decrement in response to repetitive nerve stimulation. The 26 data sets were divided into an anti-RyR-positive group (n=12) and an anti-RyR-negative group (n=14). RESULTS: Masseteric ECCT was significantly longer (p=0.017) in anti-RyR-positive group (median, mean, range; 3.6, 3.8, 3.0-5.9 ms) than in anti-RyR-negative group (3.1, 3.1, 2.7-4.0) although there were no significant differences in masseteric CMAP amplitude and % decrement between the two groups. The bite force was significantly lower in anti-RyR-positive group than in normal controls. CONCLUSIONS: Presence of anti-RyR antibodies is associated with significantly prolonged masseteric ECCT compared to absence of the antibodies in MG. SIGNIFICANCE: Anti-RyR antibody contributes to E-C coupling impairment in the masseter muscle in patients with MG.

Relationship between dysphagia and depressive states in patients with Parkinson's disease.

Aspiration pneumonia related to dysphagia is known to be the leading cause of death in patients with Parkinson's disease (PD). We investigated the relationship between depressive states and dysphagia in patients with PD. A hundred and twenty-seven PD patients gave their informed consent and were enrolled in this study. We used the Beck Depression Inventory (BDI) questionnaire to determine the participants' depressive states, and also used a questionnaire to assess participants' state of dysphagia. Participants were divided into four groups according to their BDI score. We compared the PD patients with Swallowing Disturbances Questionnaire (SDQ) scores of more than or equal to 11 with the SDQ scores of less than 11 regarding depressive categories. A logistic regression analysis was conducted to calculate odds ratios (ORs) and their 95% confidence intervals (95%CI) adjusting for age, sex, disease duration, wearing-off phenomenon and severity of movement disorder. OR (95%CI) of depressive categories, in which the trivial class was set as a reference group, were 3.28 (0.93-11.55), 13.44 (3.10-58.16), 30.35 (5.65-162.97) in the mild class, the moderate class and the severe class, respectively. This study suggests that there may be a strong relationship between depressive states and dysphagia in patients with PD.

Correlation of bite force with excitation-contraction coupling time of the masseter in myasthenia gravis.

OBJECTIVE: The aim of this study was to elucidate the relationship between the impairment of excitation-contraction (E-C) coupling of masseter and the bite force in patients with myasthenia gravis (MG). METHODS: In 20 patients with MG, masseteric compound muscle action potential (CMAP) and mandibular movement-related potentials (MRP) were recorded simultaneously after stimulating the trigeminal motor nerve with a needle electrode. The E-C coupling time (ECCT) was calculated by the latency difference between CMAP and MRP. Bite force was measured using a pressure-sensitive sheet. Serial assessments of % decrement in masseteric repetitive nerve stimulation (RNS), ECCT, and bite force were performed before and after corticosteroid therapy alone or in various combinations with FK506, cyclosporin A, intravenous immunoglobulin and immunoabsorption. RESULTS: Percent amplitude decrement in RNS and ECCT decreased significantly accompanying an increase in bite force after treatment. Simple regression analysis demonstrated a linear correlation among % decrement, ECCT and bite force. However, ECCT shortening accompanying bite force recovery without reduction in % decrement was observed in 4 patients. CONCLUSIONS: Masseteric E-C coupling is impaired in some MG patients, and functional recovery of E-C coupling contributes at least in part to the increase in bite force after treatment. SIGNIFICANCE: Impaired E-C coupling contributes to muscle weakness in patients with MG.

Response of serum carboxylated and undercarboxylated osteocalcin to risedronate monotherapy and combined therapy with vitamin K(2) in corticosteroid-treated patients: a pilot study.

OBJECTIVE: The aim of this study was to investigate the responses of serum osteocalcin (OC), undercarboxylated osteocalcin (ucOC) and N-terminal telopeptide of type I collagen (NTx) to corticosteroids, and to examine the effects of risedronate therapy with or without vitamin K(2) supplementation on bone metabolic markers in corticosteroid-treated patients. METHODS: Sixteen patients on corticosteroid therapy for neuromuscular disorders were assigned randomly to 2 groups (A: risedronate monotherapy, n=8; B: combined risedronate and vitamin K(2) therapy, n=8) and treated for 1 year. Another 6 patients who received intravenous steroid pulse therapy were assigned to group C for investigation of the effects of corticosteroids on OC and ucOC 1 month after pulse therapy. RESULTS: Serial measurements revealed that significant decreases of OC, ucOC and NTx persisted with a similar time course profile during 1 year of treatment in groups A and B, and between-group analysis failed to demonstrate any additional effects of vitamin K(2) on risedronate therapy. Intravenous steroid pulse therapy induced a transient depression of OC and ucOC within 1 week in group C. CONCLUSION: These results indicate that serum concentrations of OC and ucOC become consistently low during corticosteroid administration despite risedronate therapy with or without vitamin K(2) supplementation, and the serum ucOC level may not be a reliable indicator of vitamin K status under corticosteroid administration.

Transient oculomotor palsy correlated with nerve enhancement on MRI in chronic inflammatory demyelinating polyneuropathy.

A 40-year-old woman was admitted to our hospital because of double vision combined with left ptosis. Although at 25 years of age she had already been diagnosed with limb weakness associated with chronic inflammatory demyelinating polyneuropathy (CIDP), she had never experienced double vision until her latest condition. Neurological examination revealed left oculomotor palsy without other cranial nerve involvement. Serial magnetic resonance imaging (MRI) studies demonstrated a temporal correlation between clinical severity of oculomotor palsy and segmental enhancement of the oculomotor nerve. Gadolinium enhancement on MRI may be a significant finding indicating relapse of oculomotor involvement of CIDP.

Lhermitte's sign in alcoholic myelopathy without portosystemic shunting: MRI evaluation.

We conducted spinal MR imaging on a 35-year-old man with Lhermitte's sign that had manifested over the previous 4 years. He had consumed more than 500 ml of whisky daily for at least 10 years. However, he did not show any evidence of severe liver disease with hepato-systemic blood shunting. Neurologic examination revealed markedly depressed sense of vibration in the feet and mild spasticity in the lower limbs, together with Lhermitte's sign. MR imaging revealed abnormal signal intensity in the posterior column spanning the whole length of the upper cervical cord, which is consistent with Lhermitte's sign.