Donghwi Park

Serum methylmalonic acid correlates with neuropathic pain in idiopathic Parkinson’s disease

Recent studies have shown a relatively higher prevalence of peripheral neuropathy in idiopathic Parkinson’s disease (IPD). The hypothesis is that prolonged levodopa exposure causes vitamin B12 deficiency, which leads to peripheral neuropathy. The aim of our study was to find the relationship between vitamin B12 and its precursor methylmalonic acid (MMA) in IPD patients with neuropathic pain. We performed a cross-sectional study by enrolling consecutive 43 patients who were clinically tested positive for F-18 FP-CIT PET and 15 patients were diagnosed with peripheral neuropathy according to the Toronto clinical scoring system (TCSS). The severity of neuropathic pain was evaluated using total neuropathy scale, revised (TNSr), and Korean Neuropathic Pain Questionnaire (KNPQ). The correlations between age, IPD duration, levodopa equivalent dose (LED), UPDRS III, vitamin B12, MMA, and homocysteine levels were assessed. The prevalence rate of peripheral neuropathy in IPD patients was 35%. Among the serums assessed, MMA levels showed a positive correlation to TNSr and KNPQ in the IPD patients with peripheral neuropathy (TNSr rxa0=xa00.882, pxa0<xa00.001, KNPQ rxa0=xa00.710, pxa0=xa00.004), while Vitamin B12 and homocysteine showed no statistically significant correlation. Our study showed a prevalence of peripheral neuropathy in 35% of Korean IPD patients. The serum MMA positively correlated with the severity of neuropathic pain and this can be used as a useful marker in assessment of peripheral neuropathy in Parkinson’s disease.

Terminal latency abnormality in amyotrophic lateral sclerosis without split hand syndrome

Amyotrophic lateral sclerosis (ALS) has a peculiar involvement pattern; clinically it is known as split hand syndrome and electrophysiologically shows abnormalities in the abductor pollicis brevis (APB)/abductor digiti minimi (ADM) ratio. The aim of this study was to find a significant electrophysiological parameter in upper limb onset ALS patients with normal APB/ADM ratio when compared to cervical spondylotic amyotrophy (CSA) and healthy controls. We retrospectively reviewed the electrophysiological results of 47 upper limb onset ALS and 42 CSA cases; 20 healthy individuals were included as controls. We included ALS and CSA patients with normal ADM/APB ratio (≥0.6, and ≤1.7), and the parameters of electrophysiological study were compared. The electrophysiological parameters of statistical significance among ALS, CSA and normal controls were: amplitude of median and ulnar nerves, the terminal latency of median nerve, F-wave latency of median and ulnar nerves, terminal latency ratio of ulnar/median nerves, and F-wave latency ratio of ulnar/median nerves (pxa0<xa00.05). Among these parameters, the terminal latency ratio of ulnar/median nerve and terminal latency of median nerve in ALS were significantly different with both of CSA and normal control (pxa0<xa00.006). The abnormality in the terminal latency of the median nerve can be partly explained by the distal motor axonal dysfunction due to sodium and potassium channel abnormalities. The hypothesis of distal axonopathy is known to play an important role in the pathogenesis of ALS causing a significant prolongation of the terminal latency in the median nerve and the ulnar/median nerve ratio.

The terminal latency of the phrenic nerve correlates with respiratory symptoms in amyotrophic lateral sclerosis

OBJECTIVEnThe aim of the study was to investigate the electrophysiological parameters in phrenic nerve conduction studies (NCS) that sensitively reflect latent respiratory insufficiency present in amyotrophic lateral sclerosis (ALS).nnnMETHODnForty-nine patients with ALS were examined, and after exclusion, 21 patients with ALS and their phrenic NCS results were reviewed. The patients were divided into two groups according to their respiratory sub-score in the ALS functional rating scale - revised (Group A, sub-score 12vs. Group B, sub-score 11). We compared the parameters of phrenic NCS between the two groups.nnnRESULTSnThere were no significant differences in the clinical characteristics between the two groups. Using a multivariate model, we found that the terminal latency of the phrenic nerve was the only parameter that was associated with early symptoms of respiratory insufficiency (p<0.05). The optimal cutoff value for the terminal latency of the phrenic nerve was 7.65ms (sensitivity 80%, specificity 68.2%).nnnCONCLUSIONnThe significantly prolonged terminal latency of the phrenic nerve in our study may reflect a profound distal motor axonal dysfunction of the phrenic nerve in patients with ALS in the early stage of respiratory insufficiency that can be used as a sensitive electrophysiological marker reflecting respiratory symptoms in ALS.nnnSIGNIFICANCEnThe terminal latency of the phrenic nerve is useful for early detection of respiratory insufficiency in patients with ALS.

Lower limb muscle magnetic resonance imaging in myotonic dystrophy type 1 correlates with the six-minute walk test and CTG repeats

The aim of this study was to elucidate correlations among clinical, genetic, and magnetic resonance imaging (MRI) data of muscles in myotonic dystrophy type 1 (DM1). We retrospectively reviewed the medical records and images of nineteen patients with DM1 from different families. We retrieved the genetic data (CTG repeats) and the clinical data, which included disease duration, creatine kinase level, sum score of manual muscle testing, modified Medical Research Council sum score, and the six-minute walk test results (6MWT). The correlation analyses showed a statistically significant correlation between the modified Medical Research Council sum score and CTG repeat numbers. Among the lower extremity muscles, 6MWT correlated most with the sum of the ankle plantar-flexors (the soleus, medial, and lateral gastrocnemius muscles). Compared to the other plantar-flexor muscles, the soleus muscle presented the highest correlation with the 6MWT. Additionally, our results showed that the CTG repeat numbers did not correlate with the 6MWT. However, it correlated with the modified Medical Research Council sum score. The ankle plantar-flexor muscles were the most severely affected muscles revealed in the whole body MRI, and presented statistically significant correlation with the 6MWT. Among the plantar-flexor muscles, the soleus muscle most influenced the 6MWT.

Diffusion tensor imaging and voxel-based morphometry reveal corticospinal tract involvement in the motor dysfunction of adult-onset myotonic dystrophy type 1

Magnetic resonance imaging (MRI) studies have demonstrated that patients with myotonic dystrophy type 1 (DM1) exhibit gray and white matter abnormalities that are correlated with various genetic and neuropsychological measures. However, few MRI studies have focused on the correlations between brain abnormalities and overall motor function including gait performance. Here, we investigated the correlations between brain abnormalities, as assessed with MRI including diffusion tensor imaging (DTI), and motor performance, as assessed with the Medical Research Council sum score (MRCSS), 6-minute walk test (6MWT), and hand grip power, in patients with DM1. Eighteen patients with DM1 and twenty healthy controls participated in this study. The MRCSS and 6MWT reflect patients’ general motor performance, particularly gait, while hand grip reflects the presence of myotonia. We found significant relationships between DTI parameters in the corticospinal tract (CST) and genetic factors and motor performance in patients with DM1. These findings suggest that CST involvement reflecting deterioration of the motor tracts may play a significant role in clinical myotonia. Further, a direct relationship between the cortical gray matter volume and DTI measures in the CST suggests that white matter abnormalities in the CST are strongly associated with volume reductions in the sensorimotor cortex of patients with DM1.

Diastolic heart dysfunction is correlated with CTG repeat length in myotonic dystrophy type 1

The aims of this study were to investigate the correlations of tri-nucleotide (CTG) repeat length with detailed echocardiography (ECHO) parameters that represent myocardial function and to find a relationship between heart function and CTG repeat length in adult-onset myotonic dystrophy type 1 (DM1). In this study, clinical data for patients with DM1, including age, onset age, CTG repeat length, Medical Research Council sum score (MRCSS), and 6-min walking test (6MWT), were recorded. In addition, ECHO parameters and cardiac conduction abnormalities were evaluated. Among the cardiac parameters, the EA ratio and left ventricular end-diastolic dimension (LVEDD) were significantly correlated with the CTG repeat length (pu2009<u20090.05). Interventricular septal thickness at end-diastole was also significantly correlated with the 6MWT in a multivariate linear regression model (pu2009<u20090.05). In conclusion, motor function (MRCSS and 6MWT) and CTG repeat length significantly correlated with LV diastolic dysfunction in patients with DM1. More emphasis should be given to diastolic dysfunction, which is currently under-recognized, when evaluating patients with DM1 with no abnormalities in routine electrocardiography studies. Lastly, well-designed and longitudinal studies are warranted to characterize and understand the pathophysiology of diastolic dysfunction in DM1.

The reversible effect of neck flexion on the somatosensory evoked potentials in patients with Hirayama disease: a preliminary study

The aim of this study was to examine and characterize the reversibility of the cervical somatosensory electrophysiological pathways during neutral and flexed neck positions. The parameters of somatosensory evoked potentials (SEPs) during neutral and flexed neck positions (N9, N13, and N20 SEP latencies; N9–N13 and N13–N20 inter-peak latencies; and the changes in N9–N13 and N13–N20 inter-peak latency during neutral and flexed neck positions) were measured in the patients with Hirayama disease (HD) and also in the healthy controls. In patients with HD, there was a significant difference in the mean value of N13–N20 inter-peak latency during the flexed neck position compared to that of the healthy controls (pu2009<u20090.05). In a multivariate logistic regression analysis, N13–N20 inter-peak latency during the flexed neck position significantly correlated with the presence of HD (pu2009<u20090.05). Collectively, in this cohort of patients with HD, the neck flexion of patients with HD showed a reversible effect on the SEP parameter, especially in N13–N20 inter-peak latency. Conventional diagnosis of HD is based on nerve conduction studies and electromyography along with a cervical flexion MRI, and our study suggests the possibility of an additional and cost-effective electrophysiological marker that may be helpful in the diagnosis of HD.

Successful IVIG treatment without discontinuation of TNF-α blocker in Guillain-Barre syndrome induced by adalimumab in patient with Crohn’s disease

Dear Editor, Crohn’s disease (CD) is a multisystemic inflammatory disorder that primarily affects the gastrointestinal tract. In cases of moderate to severe CD, anti-tumor necrosis factor (TNF)-α blockers monotherapy is strongly recommended by most guidelines in order to induce and maintain remission. Although these drugs are well tolerated and safe, rarely adverse events are reported, such as Guillain-Barre syndrome (GBS). GBS is a rare disease which can cause severe and irreversible damage to the patient, and withdrawal of antiTNF-α therapy is recommended when these adverse effects occur [1]. Adalimumab is one of the anti-TNF-α blockers which is commonly used in management of CD. To the best of our knowledge, there has been no report that has investigated continued use of adalimumab while treating GBS with intravenous immunoglobulin (IVIG) and its consequences. Although there have been a few case reports related to adalimumab-associated GBS in patients with CD, in these cases, adalimumab was immediately suspended, as recommended by the current treatment guidelines [1]. The patient was a 33-year-old woman who was diagnosed as CD at the age of 19 and who was suffering gastrointestinal (GI) symptoms, such as chronic diarrhea and hematochezia. The patient was treated with prednisolone 40 mg and mesalazine 4000 mg for 1 month and her symptoms improved, but she stopped taking prednisolone due to side effects, such as moon face and generalized edema. After that, she was on 20 mg of prednisolone and 4000 mg of mesalazine irregularly for 13 years at the time of symptom exacerbation. One week before the start of treatment with adalimumab, her GI symptoms became worse, and an immunosuppressant (150 mg of azathioprine) was prescribed for management of CD. However, it also stopped due to nausea and vomiting. After the failure of these conventional therapies due to side effects, she was prescribed a subcutaneous injection of adalimumab 40 mg every 2 weeks. After treatment with adalimumab, her GI symptoms improved, but weakness of both the upper and lower extremities occurred, along with sensory loss, which started from the lower limbs just after the fourth injection of adalimumab (2 months after treatment with adalimumab). She was admitted to the neurology department of our hospital for further evaluation and treatment. The initial neurological examination at admission showed normal cranial nerve functions, but the deep tendon reflex of both the upper and lower limbs decreased. The motor power of both the distal upper and lower extremities showed a profound weakness, rated as medical research council (MRC) grade 1, and both proximal upper and lower extremities were MRC grade 2 [2, 3]. In addition, the proprioception and pinprick sensation of both the upper and lower extremities were also decreased. A brain and whole spine MRI performed during admission showed no abnormal findings. However, a nerve conduction study showed markedly reduced compound muscle action potential (CMAP) amplitude in the motor nerves without significant slowing of the motor velocities, which was suggestive of a severe axonal loss. The F wave and H reflex * Donghwi Park bdome@hanmail.net

Recurrent complex regional pain syndrome type I in a patient with amyotrophic lateral sclerosis: a case report

Dear Editor, Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease that involves limb, axial, bulbar, and respiratory muscles [1]. ALS involves degeneration of the motor system combining upper and lower motor neuron signs [1, 2]. Although sensory or dysautonomic signs are not clinically evident, pain can occur in these patients. However, it is usually secondary to severe paresis and immobility, such as frozen shoulder resulting from severe upper limb paresis [2]. In previous research, there have been several reports about ALS patients with complex regional pain syndrome (CRPS) [1, 2]. To the best of our knowledge, however, there has been no report about recurrent complex regional pain syndrome in patients with ALS. Here, therefore, we report on an ALS patient with recurrent CRPS, which seemed to be caused by adhesive capsulitis.

A novel CACNA1A mutation associated with episodic ataxia 2 presenting with periodic paralysis

Episodic ataxia type 2 (EA2: OMIM#108500) is a genetic condition caused by mutation in the voltage-dependent calcium channel gene CACNA1A. EA2 is clinically characterized by vertigo, nystagmus, and ataxia that ensue for several hours. Patients with EA2 are known to have a good response to acetazolamide. We report a case of a novel CACNA1A gene mutation in a patient who initially presented with periodic paralysis.