Reductions in muscle quality and quantity in chronic inflammatory demyelinating polyneuropathy patients assessed by magnetic resonance imaging

Introduction: Weakness in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) may be caused by decreases in muscle quantity and quality, but this has not been explored. Methods: Twelve patients with CIDP (mean age 61 years) and 10 age‐matched (mean age 59 years) control subjects were assessed for ankle dorsiflexion strength, and two different MRI scans (T1 and T2) of leg musculature. Results: Isometric strength was 36% lower in CIDP patients compared with controls. Tibialis anterior muscle volumes of CIDP patients were smaller by ～17% compared with controls, and non‐contractile tissue volume was ～58% greater in CIDP patients. When normalized to total muscle or corrected contractile volume, strength was ～29% and ～18% lower, respectively, in CIDP patients. Discussion: These results provide insight into the structural integrity of muscle contractile proteins and pathologic changes to whole‐muscle tissue composition that contribute to impaired muscle function in CIDP. Muscle Nerve 58 : 396–401, 2018     

Association of muscle strength and electrophysiological measures of reinnervation in diabetic neuropathy

Motor function was assessed in 34 non-insulin-dependent and 19 insulin-dependent diabetic patients with macroelectromyography and isokinetic dynamometry. Fiber density (FD) and the amplitude of the macro motor unit potential (macro MUP) of the anterior tibial and lateral vastus muscles were obtained and maximal isokinetic strength of the ankle and knee extensors were determined. All patients underwent standardized clinical examination including a neurological disability score (NDS), quantitative sensory examination, and conventional motor nerve conduction studies. The amplitude of the macro MUP and FD of the anterior tibial muscle were increased in neuropathic patients without weakness (P < 0.05) and further increased in neuropathic patients with weakness (P < 0.05). The NDS was related to the FD and the amplitude of the macro MUP for the anterior tibial and lateral vastus muscle [r = 0.55–0.75 (P < 0.005)]. Muscle strength of ankle and knee extensors correlated with the FD [r = −0.69 (P < 0.0001) and r = −0.58 (P < 0.001), respectively] and with the amplitude of the macro MUP of the two muscles [r = −0.63 (P < 0.0001) and r = −0.37 (P < 0.05), respectively]. Our findings support the hypothesis that loss of muscle strength in diabetic patients is due to incomplete reinnervation following axonal loss. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1647–1654, 1998     

Assessment of contractile and noncontractile components in human skeletal muscle by magnetic resonance imaging

A magnetic resonance imaging (MRI) technique for the assessment of contractile and noncontractile components of human skeletal muscle is described, and the inter-rater and intra-rater test-retest reliability for repeated measurements from the same MR image are examined. Twenty cross-sectional MR images from the right lower leg were obtained from 30 healthy young men and women (mean age 24.1 years, SD 3.3). The anatomical cross-sectional area (aCSA; cm2), the cross-sectional area of noncontractile components (Noncon; cm2), the contractile cross-sectional area (cCSA = aCSA minus Noncon; cm2), and the relative amount of Noncon (%), of the ankle dorsiflexor muscle compartment were determined for each slice using a computer-based image analysis system. Reliability for repeated measurements of the slice with the largest aCSA for the 30 subjects was analyzed by two raters on two different occasions. Inter-rater reliability on both occasions, assessed by the intraclass correlation coefficient (ICC), was excellent for cCSA (ICC3.1 = 0.99) and Noncon (ICC(3.1) > 0.82). Intra-rater (between occasions) reliability was excellent for the two raters for measurements of cCSA (ICC1.1 = 0.99) and Noncon (ICC1.1 > 0.94). Bland and Altman analyses did not identify any clinically relevant bias in the measurements. Method errors were acceptable: within subjects coefficients of variation (CV) was less than 1.8% for cCSA and less than 16.3% for Noncon. It is concluded that repeated measurements of contractile and noncontractile components of the ankle dorsiflexor muscle compartment, obtained from the same MR image, are highly reliable.     

Study of visual evoked potentials in diabetics without retinopathy: correlations with clinical findings and polyneuropathy

To evaluate central optic pathways' involvement in diabetics, visual evoked potentials (VEP), in particular the latency of positive peak (LP100), were studied in 35 patients without retinopathy (4 insulin-dependent, 31 non-insulin-dependent) and 35 normal controls using reversal pattern stimulation. LP100 was significantly delayed in diabetics at both binocular and monocular stimulation. Furthermore, the delay in LP100 was significantly longer in the diabetics with polyneuropathy than in those without, particularly after binocular stimulation. A positive correlation was found between latencies of VEP and HbA1, duration of disease, and neurologic score. VEP measurement seems a simple and sensitive method for detecting early alterations in central optic pathways in diabetics.     

Thigh muscle function in stroke patients revealed by velocity-encoded cine phase-contrast magnetic resonance imaging

Current methods of clinical assessment of muscle coordination and function after stroke do not provide information on deep muscles. The objective of this study was to examine how stroke affects both superficial and deep muscles' coordination and whether muscle function improves after rehabilitation. Muscle function, coordination, and activity of quadriceps femoris (QF) and hamstrings were evaluated in 10 stroke patients with mild hemiparesis and in 6 controls using velocity-encoded cine phase-contrast magnetic resonance imaging (VE-PC MRI), surface electromyography (sEMG), and maximal voluntary isometric contraction torque (MVC). At baseline, the peak muscle velocity of the rectus femoris (RF) and the ratio between the peak velocities of the RF and vasti were lower in the affected limb (AL) of stroke patients than in controls. Co-contraction of agonists and antagonists was higher in the AL than in controls. Muscle activity measured by sEMG showed similar behavior. After rehabilitation, the activity ratio of hamstrings and adductors to QF decreased slightly toward normal so there were no significant differences between the AL and controls. Impaired biarticular RF muscle function in stroke patients is the limiting factor during knee extension-flexion movements. After rehabilitation, improved functional performance was partly explained by the fact that the activities of the RF and vasti became more synchronized. VE-PC MRI can provide quantitative in vivo measurements of both superficial and deep muscles, and the information acquired after stroke can be utilized to render therapy more efficient and individually tailored.     

Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non‐classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.     

Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography

Background and objectives

Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders. While peripheral nerve involvement is frequent in spastic paraplegia 7 (SPG7), the evidence of peripheral nerve involvement in SPG4 is more controversial. We aimed to characterize lower extremity peripheral nerve involvement in SPG4 and SPG7 by quantitative magnetic resonance neurography (MRN).

Methods

Twenty-six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age-/sex-matched healthy controls prospectively underwent high-resolution MRN with large coverage of the sciatic and tibial nerve. Dual-echo turbo-spin-echo sequences with spectral fat-saturation were utilized for T2-relaxometry and morphometric quantification, while two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments.

Results

All microstructural (proton spin density [ρ], T2-relaxation time, magnetization transfer ratio) and morphometric (cross-sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. ρ was superior in differentiating subgroups and identifying subclinical nerve damage in SPG4 and SPG7 without neurophysiologic signs of polyneuropathy. MRN markers correlated well with clinical scores and electroneurographic results.

Conclusions

MRN characterizes peripheral nerve involvement in SPG4 and SPG7 as a neuropathy with predominant axonal loss. Evidence of peripheral nerve involvement in SPG4 and SPG7, even without electroneurographically manifest polyneuropathy, and the good correlation of MRN markers with clinical measures of disease progression, challenge the traditional view of the existence of HSPs with isolated pyramidal signs and suggest MRN markers as potential progression biomarkers in HSP.     

Safety and efficacy of ranirestat in patients with mild‐to‐moderate diabetic sensorimotor polyneuropathy

We examined the efficacy and safety of ranirestat in patients with diabetic sensorimotor polyneuropathy (DSPN). Patients (18–75 years) with stable type 1/2 diabetes mellitus and DSPN were eligible for this global, double‐blind, phase II/III study ( ClinicalTrials.gov NCT00927914). Patients (n = 800) were randomized 1 : 1 : 1 to placebo, ranirestat 40 mg/day or 80 mg/day (265 : 264 : 271). Change in peroneal motor nerve conduction velocity (PMNCV) from baseline to 24 months was the primary endpoint with a goal improvement vs. placebo ≥1.2 m/s. Other endpoints included symptoms, quality‐of‐life, and safety. Six hundred thirty‐three patients completed the study. The PMNCV difference from placebo was significant at 6, 12, and 18 months in both ranirestat groups, but <1.2 m/s. The mean improvement from baseline at 24 months was +0.49, +0.95, and +0.90 m/s for placebo, ranirestat 40 mg and 80 mg, respectively (NS). The treatment difference vs. placebo reached significance when ranirestat groups were combined in a post hoc analysis (+0.44 m/s; p = 0.0237). There was no effect of ranirestat on safety assessments, secondary or exploratory endpoints vs. placebo. Ranirestat was well tolerated and improved PMNCV, but did not achieve any efficacy endpoints. The absence of PMNCV worsening in the placebo group underscores the challenges of DSPN studies in patients with well‐controlled diabetes.     

Altered T2* relaxation time of the hippocampus in major depressive disorder: Implications of ultra-high field magnetic resonance imaging

Previous studies with 1.5 T or 3.0 T magnetic resonance imaging (MRI) have produced mixed results regarding the structural changes of the hippocampus in major depressive disorder (MDD). Subtle region-specific hippocampal tissue changes might be more sensitively detected by measuring the T2* relaxation time (T2*-RT) by ultra-high-field (UHF) MRI, as it provides much higher contrast and sensitivity and consequently greater resolution. We assessed the T2*-RTs of hippocampal sub-regions in 16 MDD patients (9 with recurrent MDD) and 16 control subjects using an UHF 7.0 T MRI system. T2*-RTs of CA1, CA2, CA3, CA4, and subiculum were calculated for both left and right hippocampus. MDD patients had significantly longer T2*-RTs in the right CA1 and subiculum than control subjects. Patients with recurrent MDD had significantly longer T2*-RTs in the right subiculum than those experiencing a first depressive episode, and longer T2*-RTs in the right CA1, CA3, and subiculum than control subjects. Values for T2*-RTs of the right CA3 were significantly correlated with illness duration. In conclusion, we report that T2*-RTs in the right subiculum and CA1 were increased in patients with MDD, especially in cases of recurrent MDD. These findings suggest that region-specific hippocampal damage may be occurring in recurrent depression.     

Nerve ultrasound in diabetic polyneuropathy: Correlation with clinical characteristics and electrodiagnostic testing

Introduction: Diabetic polyneuropathy (DPN) is increasingly prevalent in the USA, but nerve ultrasound (US) findings have not been assessed systematically. Our aim was to establish the sonographic characteristics of lower extremity nerves in DPN and correlate them with electrodiagnostic (EDx) findings. Methods: Consecutive patients (n = 25) with evidence of DPN and 25 patient controls without DPN underwent blinded US imaging of the fibular and sural nerves. Nerve cross‐sectional area (CSA), diameter and echogenicity were recorded. Results: There were no differences in fibular or sural nerve CSA, diameter, or echogenicity between the 2 groups. No correlations between nerve CSA and EDx studies were found. In DPN, there were moderate inverse correlations with age (r = ?0.44 sural ankle, r = ?0.39 sural leg, r = ?0.45 fibular ankle). Conclusions: US measurements of lower extremity nerves in DPN do not differ from controls or correlate with EDx findings. Novel US techniques and/or pedal nerve US may be necessary to detect differences. Muscle Nerve 47:379‐384, 2013     

Objective quantification of muscle and fat in human dystrophic muscle by magnetic resonance image analysis

Information about changes in muscle composition has to date been primarily restricted to histological examination of biopsy samples or qualitative assessment of images obtained using a variety of techniques (e.g., ultrasound, CT, and MRI). We describe the development of a quantitative method for the analysis of muscle composition using MR T₂ relaxation time mapping and image analysis. This approach provides an objective means of studying muscle and, when used in conjunction with force production measurements, may provide an accurate measure of response to muscle therapy. © 1996 John Wiley & Sons, Inc.     

Prostaglandin E1 in conjunction with high doses of vitamin B12 improves nerve conduction velocity of patients with diabetic peripheral neuropathy

BACKGROUND： Prostaglandin El improves diabetic peripheral neuropathy in symptoms and sensory threshold. Vitamin Bi and methyl-vitamin BI2 improve microcirculation to peripheral nerve tissue and promote neurotrophy. OBJECTIVE： To observe motor nerve and sensory nerve conduction velocity in patients with diabetic peripheral neuropathy, prior to and after treatment with prostaglandin El, vitamin B I and different doses of vitamin B 12. DESIGN, TIME AND SETTING： Randomized, controlled experiment, performed at the Department of Neurology, Beijing Hantian Central Hospital, between February 2002 and September 2007. PARTICIPANTS： A total of 122 patients with type 2 diabetic peripheral neuropathy; 73 males and 49 females were included. All patients met the diagnostic criteria of diabetes mellitus, as determined by the World Health Organization in 1999 and 2006, and also the diagnostic criteria of diabetic peripheral neuropathy. For each subject, conduction disorders in the median nerve and in the common peroneal nerve were observed using electromyogram. Also, after diet and drug treatment, the blood glucose level of subjects was observed to be at a satisfactory level for more than two weeks, and the symptoms of diabetic peripheral neuropathy were not alleviated. METHODS： All patients were randomly divided into the following three groups. A control group （n = 40）, in which, 100 mg vitamin B1 and 500 μg vitamin BI2 were intramuscularly injected. A vitamin B12 low-dose treated group （ n = 42）, in which 10 μ g prostaglandin E1 in 250 mL physiological saline was intravenously injected once a day and 100 mg vitamin BI and 500 11 g vitamin BI2 was intramuscularly injected once a day. Lastly, a vitamin B12 high-dose treated group （n = 40）, in which administration was the same as in the vitamin B12 low-dose treated group, except that 500 11 g vitamin BI2 was replaced by 1mg vitamin B12. Administration was performed for four weeks for each group. MAIN OUTCOME MEASURES： The motor nerve and sensory nerve con     

Ultrasound, computed tomography and magnetic resonance imaging in myopathies: correlations with electromyography and histopathology

Imaging of examinations by ultrasound (US), computerized tomography (CT) and low field magnetic resonance imaging (MRI) were compared with EMG and muscle biopsy findings in the same muscles of 33 patients with different neuromuscular diseases. None of the imaging methods revealed specific diagnostic details, but gave valuable information on the extent and distribution of muscle involvement. In myopathies all imaging modalities corresponded well with the EMG and histopathology findings, but in the neuropathies with minimal tissue destruction EMG was, understandably, more sensitive. The imaging characteristics of MR were as good as those of CT, but MRI has the advantage of not requiring ionizing radiation. US is the most economical method and it was found to be, despite its lower resolution, very informative in the hands of an experienced examiner, especially for the detection of fibrosis. The good agreement of histopathology with pathologic imaging and EMG findings implies that the accuracy of muscle biopsy increases, if its site is selected on the basis of imaging and/or EMG examination.     

Clinical and magnetic resonance imaging findings of HIV-Negative patients with neurosyphilis

There have been no serial studies about neuroradiological findings of neurosyphilis in the literature. There have been only case reports concerning HIV negative patients with neurosyphilis. We present 8 HIV negative neurosyphilis patients two of whom are women. The mean age of the patients was 48 years±12.37. Five of the 8 patients had general paresis, two optic atrophy and one multiple cranial neuropathies. The CSF findings were quite similar in 6 of 8 patients. In half of the patients cranial MRI showed mild cerebral atrophy. Nonspecific hyperintense small foci in 3 patients are thought to be related to syphilis. Hyperintensity involving bilateral medial and anterior temporal regions more prominent on the left side was seen in one of the patients with general paresis. This finding may be due to cytotoxic edema associated with status epilepticus and may mimic herpes simplex and other limbic encephalitides. Though not typical, certain MRI findings guides for the diagnosis of neurosyphilis. Received in revised form: 5 April 2006     

The effect of gastric secretion on gastric physiology and emptying in the fasted and fed state assessed by magnetic resonance imaging

Abstract Conventional measurement of gastric secretion is invasive and cannot assess the intra‐gastric distribution of gastric contents or the effects of secretion on gastric function. This study assessed the effect of gastric secretion on gastric volume responses and emptying (GE) using a validated fast T₁ mapping magnetic resonance imaging (MRI) technique. Twelve healthy participants were studied in the fasted state and after 200 kcal Gadolinium‐DOTA labelled glucose meal during intravenous infusion of pentagastrin or placebo in double‐blind, randomized order. Total gastric volume (TGV) and gastric content volume (GCV) was assessed by MRI volume scans and secretion by fast T₁ mapping. Data was described by the κ‐coefficient (volume change after meal ingestion), by GE half time (T₅₀) and maximal GE rate (GER_max) derived all from a GE model. Pentagastrin increased GCV and TGV compared to placebo [κ(GCV):1.6 ± 0.1 vs 0.6 ± 0.1; κ(TGV): 1.6 ± 0.1 vs 0.7 ± 0.1; P < 0.001]. T₁ maps revealed a secretion layer above the meal, the volume of which was associated with κ (R² = 83%, P < 0.001). TGV and GCV change were similar in both conditions (κ; P = ns). T₅₀ was higher for pentagastrin than for placebo (84 ± 7 vs 56 ± 4min, P < 0.001); however, GER_max was similar (5.9 ± 0.6 vs 4.9 ± 0.4 mL min^?1, P = ns). This study shows volume and distribution of gastric secretion can be quantified in‐vivo by non‐invasive MRI T₁ mapping. Increased GCV drove TGV accommodation without evidence of a direct effect of pentagastrin or excess acid on gastric function. Secretion increases GCV thus prolongs GE as assessed by T₅₀; however, GE rate is unchanged.     

Spin-lock magnetic resonance imaging of muscle in patients with autosomal recessive limb girdle muscular dystrophy.

Spin-lock imaging is a new magnetic resonance imaging (MRI) technique used to reflect the microstructural integrity of muscle. The purpose of this study was to characterize spin-lock contrast (SLC) of calf muscles in limb girdle muscular dystrophy (LGMD). The calf muscles of 5 patients with LGMD and 10 healthy volunteers were imaged with an off-resonance magnetic resonance (MR) spin-lock suppression pulse. Spin-lock suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles. Clinical assessments of muscle strength were compared to the spin-lock suppression ratios in the LGMD group. Strong SLC was observed in healthy muscles, with mean (+/- SD) suppression ratios ranging from 51.2% (+/- 3.6%) to 56.3% (+/- 1.3%). In diseased muscle, spin-lock signal suppression was reduced by 8%-70%, demonstrating an inverse correlation between symptom duration and suppression ratios. Spin-lock contrast in the patients with LGMD, as a reflection of tissue integrity, was best preserved in posterior tibialis, anterior tibialis, soleus, and gastrocnemius muscles in descending order. Clinical assessments did a poorer job of differentiating than SLC did and were in poor agreement with spin-lock suppression ratios. Spin-lock MRI can quantify microstructural changes in LGMD and appears to provide information not obtainable from clinical evaluations. This suggests that this noninvasive technique may be useful in evaluating the extent, progression, and response to therapy of LGMD.