Yoshihiko Furusawa

Long-term effect of repeated lidocaine injections into the external oblique for upper camptocormia in Parkinson's disease

BACKGROUND Parkinsons disease (PD) is occasionally complicated by camptocormia. In a previous study, we classified camptocormia into upper and lower types based on the inflection point, and reported that lidocaine injection into the external oblique muscle, but not into the internal oblique or rectus abdomen, improved upper camptocormia in PD. The effect of a single lidocaine injection disappeared over a period of few days. In this study, we used repeated lidocaine injections into the external oblique for 4-5 days and evaluated the effects of such treatment for up to 90 days. METHODS The study subjects were 12 patients with PD and upper camptocormia who were treated with repeated lidocaine injections into the bilateral external oblique followed by rehabilitation. The effect of treatment was evaluated by measuring the angle of truncal flexion before and after the injection. Patients who showed improvement with repeated injections were evaluated during a 90-day period. RESULTS Eight out of 12 patients showed significant improvement in posture after a single lidocaine injection. However, the effect subsided several days after treatment. Repeated injections produced long-term improvement in 9 out of 12 patients, which was maintained during the 90-day observation period in eight of these patients. CONCLUSIONS Our results showed that repeated lidocaine injections into the external oblique improved upper camptocormia, and that the effect was maintained in the majority of patients during the 90-day observation period, indicating that repeated lidocaine injections into the external oblique have therapeutic effect on upper camptocormia in patients with Parkinsons disease.

Role of the external oblique muscle in upper camptocormia for patients with Parkinson's disease†‡

Patients with Parkinson’s disease (PD) often experience camptocormia, a postural disorder with unclear pathophysiology and unestablished treatments. We clinically categorized camptocormia as upper and lower types based on the location of inflection points. We defined upper camptocormia as abnormal truncal flexion at a point between the lower thoracic and upper lumbar vertebrae whose flexion angle exceeded 40 degrees, whereas lower camptocormia was defined as abnormal truncal flexion at the hip joint. This study focused on upper camptocormia. We performed lidocaine injections into the abdominal muscles of PD patients with upper camptocormia and evaluated their effects on posture to investigate its pathophysiology. Patients with fixed posture because of spinal disease or truncal muscle weakness were excluded. We included 5 patients (4 women and 1 man; mean age, 70.8 6 4.4 years; PD duration, 8.2 6 3.9 years; Hoehn & Yahr stage, 2.6 6 0.8) treated with antiparkinson drugs in our hospital. Camptocormia did not respond to these drugs in any of the patients. Ultrasound guidance was used for lidocaine injections into the abdominal muscle (rectus abdomen [RA] and external oblique [EO] in all patients; internal oblique [IO] in 2 patients; 50 mg in each muscle bilaterally). Although the order of each injection was different in each patient, the following injection was performed on confirming that improvement diminished or if no improvement was observed after several days. Flexion angles were measured before and after each injection. The angle formed between a line perpendicular to the ground and a line linking the C7 vertebra with the inflection point of the trunk was defined as the flexion angle. This study was approved by the NCNP ethics committee. Informed consent was obtained from all patients. The posture of all patients improved following injection into the EO. The average flexion angle decreased from 49 6 6.0 degrees to 37 6 10 degrees (truncal angle of agematched PD patients without camptocormia was 29.4 6 3.7 degrees; Fig. 1), Only 1 patient showed mild improvement after injection into the RA. No improvements were observed following injection into the IO. The RA performs truncal anteflexion, whereas the EO and IO work bilaterally for truncal flexion. Azher et al previously reported improvement of camptocormia by botulinum toxin injection into the RA, although they did not classify camptocormia by type. In the present study, forward flexion was reduced in all patients after injection into the EO, not RA nor IO. Our results may suggest that the EO is primarily associated with upper camptocormia pathogenesis. Considering that previous studies have speculated that lidocaine could suppress dystonic excitation, dystonia of the EO may be a cause of upper camptocormia. Although this study has some limitations, such as the small number of patients and not adjusting lidocaine dose for muscle size, this is the first report to investigate camptocormia pathophysiology by classification, and these findings may contribute to the treatment of upper camptocormia in patients with PD. To confirm our results, we have been carrying out a larger study.

Mechanism of camptocormia in Parkinson's disease analyzed by tilt table-EMG recording

BACKGROUND We previously classified camptocormia of Parkinsons disease (PD) into upper and lower types based on the inflection point, and reported improvement of upper camptocormia after lidocaine injection into the external oblique. However, the exact pathophysiology of this phenomenon remains obscure. METHODS Surface electromyography (sEMG) was recorded in 11 PD patients with upper camptocormia, 11 PD patients with lower camptocormia, and 10 age-matched PD patients without postural deformity. Electrodes were positioned above the external oblique, hip flexors and paraspinal muscles at Th11 level bilaterally. Recording commenced with the patient in supine position on a tilt table, and continued when the table was tilted up to vertical position. Lidocaine was injected into the external oblique in patients with upper camptocormia and the psoas major in patients with lower camptocormia. RESULTS All patients with upper and lower camptocormia developed the corresponding camptocormic posture during tilt up. The onset of camptocormic posture was preceded by the appearance of sEMG activity in the external oblique in 10 out of 11 patients with upper camptocormia, but less frequently in patients with lower camptocormia and the controls. Hip flexors sEMG activity was recorded in almost all patients. Posture was improved in 8 out of 9 patients with upper camptocormia, and 9 out of 11 patients with lower camptocormia following injections of lidocaine. CONCLUSIONS The results suggest the external oblique is involved, at least in part, in the development of upper camptocormia. Although EMG findings cannot differentiate pathogenicity, the psoas major is probably involved in lower camptocormia.

Late-onset Pompe disease after 4 years of enzyme replacement therapy: An autopsy case

We report an autopsy case of advanced late‐onset Pompe disease (juvenile type). At 15 years‐of‐age, the patient experienced proximal weakness and subsequently required non‐invasive positive pressure ventilation. Enzyme replacement therapy was initiated at 37 years‐of‐age, which improved pinch power and alleviated respiratory distress. At age 41 years, repetitive pneumothorax led to respiratory failure and death. Autopsy excluding the brain showed few vacuoles and periodic acid–Schiff‐positive fibers in the left rectus femoris, compared with the contralateral muscle biopsy carried out at 21 years‐of‐age. Vacuolar changes were also less evident than previous autopsy cases without enzyme replacement therapy. The findings suggest that enzyme replacement therapy might have suppressed myovacuolopathy in our patient with advanced late‐onset Pompe disease. Apart from vacuolopathy, the autopsied muscle showed marked myofiber atrophy and fibrosis, suggesting that disuse atrophy could have contributed to the muscle weakness.

Major depression: what caused the crisis?

In July, 2008, a 67-year-old woman with refractory depression was referred to our institute. In 2006, she had a thymectomy for thymoma. In January, 2008, after experiencing family discord, she lost her appetite, and her bodyweight decreased by 5 kg in 1 month. She became pessimistic and self-recriminating and made several suicide attempts. CT showed no evidence of a recurrence of the thymoma. Neurological examination showed only slight muscle weakness of her limbs, but the cause of her anorexia remained unclear despite further in-hospital examinations such as gastrointestinal tract endoscopies and systemic contrast-enhanced CT. She was diagnosed as having depression and was transferred to a regional psychiatric hospital, where she was treated sequentially with sertraline, paroxetine, clomipramine, and nortrip tyline, and augmentation lithium. These treatments were ineff ective, and her body weight decreased from 60 kg to 33·5 kg. She was then transferred to us. Her depressed mood, decreased interests, hypogeusia, anorexia, insomnia, anxious restlessness, decreased energy and fatigue, guilty feelings, poor concentration, and suicidal ideation persisted. She fulfi lled the DSM-IV diagnostic criteria for major depressive disorder. Her total score on the 17-item Hamilton Depression Rating Scale (total-HDRS) was 40. She could walk and had no ocular and bulbar symptoms, but neurological examinations showed mild proximal muscle weakness and atrophy of her limbs. Blood test results indicated hypoalbuminaemia (albumin 3·4 g/dL); other investi gations including CT chest, tumour markers, electro encephalography, and brain MRI were normal. Ten sessions of electroconvulsive therapy (ECT) were done in September, but the depressive symptoms persisted. She stopped taking medication, other than quetiapine as required (prescribed by us), but at the end of October, she suddenly developed impaired con sciousness with a reduced respiratory rate. A blood gas analysis showed carbon dioxide narcosis, and she was immediately placed on a ventilator. No evidence of pulmonary disease was found, and a diagnosis of myasthenic crisis was made on the basis of a high acetylcholine receptor antibody (AchR-Ab) titre (120 nmol/L), waning on the Harvey-Masland test, and a history of thymoma. She was treated with plasmapheresis and immunoadsorption followed by prednisolone treatment (maximum dose, 50 mg/day). Her respiratory function subsequently improved, and she was extubated. In December, she was treated with pyridostigmine (180 mg/day). As the anti-AchR-Ab titre decreased, totalHDRS score improved substantially without antidepressant therapy (fi gure). Her long-lasting depressive symptoms improved completely, and her bodyweight recovered to 40 kg; she was discharged in July, 2009. When last seen in September, 2009, both her depression and myasthenia gravis were in remission. The pathology of depressive symptoms associated with myasthenia gravis, including the hypothalamo-pituitaryadrenal axis dysfunction resulting from chronic stress and central cholinergic defi cit, is controversial and remains to be elucidated. Although some patients with major depressive disorder complicated with myasthenia gravis improve after ECT, the potential to misdiagnose myasthenia gravis as depression has been highlighted. 20% of people with myasthenia gravis are initially diagnosed as having a psychiatric disorder, and improvements in depressive symptoms associated with improvements in myasthenia gravis have been reported. Whether depressive symptoms in individual cases are attributable to myasthenia gravis or major depressive disorder should be investigated. Since the AchR-Ab titre and the depressive symptoms improved over time in our case, we concluded that the patient’s depressive symptoms could predominantly be attributed to myasthenia gravis. When managing treatment-resistant depressive patients, the medical history must be suffi ciently considered.

Dysphagia Causes Symptom Fluctuations after Oral L-DOPA Treatment in a Patient with Parkinson Disease

Objective: The causes of “delayed-on” and “no-on” phenomena in Parkinson disease (PD) are thought to have some impact on the progress of L-DOPA from the time of ingestion until it reaches the brain and is converted to dopamine. Dysphagia can cause fluctuating symptom expression in L-DOPA therapy for PD. Case Description: A 69-year-old man with PD presented with “delayed-on” and “no-on” phenomena. The patient developed a gait disorder at age 60 years, and he began coughing on his food during breakfast at age 64 years. Even though he was independent in daily life, he could not eat because of dysphagia in an “off” state. Videofluoroscopic examination of swallowing in an “off” state revealed bradykinesia of the tongue and the retention of tablets in the epiglottic vallecula. We trained him to keep his tongue in strong contact with the upper incisors before swallowing. After rehabilitation of dysphagia, the frequency of “delayed-on” and “no-on” phenomena decreased, and his peak L-DOPA plasma concentration was elevated. Additionally, transdermal rotigotine (RTG) was initiated at a maintenance dose of 9.0 mg. The patient reported improvement in swallowing, and the frequency of “no-on” phenomena decreased. Conclusion: In PD patients, the “no-on” phenomenon can be caused by posterior contractile dysfunction of the tongue, and it can be improved with training of the tongue and transdermal RTG administration.

42. A 61-year-old man with lesions in multiple left nerve roots and dorsal root ganglia initially presented with weakness of the left hallux flexion

Our previous studies suggest that spinal cord injury (SCI) patients show a decreased representation of activation in the primary motor area during toes’ movements. But these representations of the premotor area (PM) and supplementary motor area (SMA) after SCI are largely unknown. The purpose of this study is to determine the premotor cortical representations during movements of toes in patients with SCI using functional Magnetic Resonance Imaging (fMRI). We enrolled 10 SCI patients and 10 healthy, age-matched controls, and they signed consent forms. All patients were diagnosed chronic complete SCI at the level of TH4-L1. fMRI of 1.5 T was used to map cortical representations associated with motor tasks of the right toes in two groups. The subjects predicted a timing when a ball that is vanished from sight reaches an end on a PC game, and they flexed toes. Patients were just required to make efforts to move toes. We compared SCI patients with controls at fMRI maps. During toes’ movements, patients showed a decreased representation of activation in SMA. However patients showed an increased representation of activation in right PM. Our results suggest that some functional changes in the motor command of SCI patients occur.