Vinay Chaudhry

Rhabdomyolysis: an evaluation of 475 hospitalized patients.

Abstract: Rhabdomyolysis is a common and potentially lethal clinical syndrome that results from acute muscle fiber necrosis with leakage of muscle constituents into blood. Myoglobinuria is the most significant consequence, leading to acute renal failure (ARF) in 15%-33% of patients with rhabdomyolysis. Rhabdomyolysis occurs from inherited diseases, toxins, muscle compression or overexertion, or inflammatory processes, among other disorders. In some cases, no cause is found. We describe 475 patients from the Johns Hopkins Hospital inpatient records between January 1993 and December 2001 for the following discharge diagnosis codes: myoglobinuria, rhabdomyolysis, myopathy, toxic myopathy, malignant hyperthermia, neuroleptic malignant syndrome, and polymyositis. Of 1362 patients, 475 patients with an acute neuromuscular illness with serum creatine kinase (CK) more than 5 times the upper limit of normal (>975 IU/L) were included. Patients with recent myocardial infarction or stroke were excluded. The etiology was assigned by chart review. For all, the highest values of serum CK, serum creatinine and urine myoglobin, hemoglobin, and red blood cells were recorded. Forty-one patients had muscle biopsy within at least 2 months from the onset of rhabdomyolysis. Of the 475 patients, 151 were female and 324 were male (median age, 47 yr; range, 4-95 yr). Exogenous toxins were the most common cause of rhabdomyolysis, with illicit drugs, alcohol, and prescribed drugs responsible for 46%. Among the medical drugs, antipsychotics, statins, zidovudine, colchicine, selective serotonin reuptake inhibitors, and lithium were the most frequently involved. In 60% of all cases, multiple factors were present. In 11% of all cases, rhabdomyolysis was recurrent. Underlying myopathy or muscle metabolic defects were responsible for 10% of cases, in which there was a high percentage of recurrence, only 1 etiologic factor, and a low incidence of ARF. In 7%, no cause was found. ARF was present in 218 (46%) patients, and 16 died (3.4%). A linear correlation was found between CK and creatinine and between multiple factors and ARF, but there was no correlation between ARF and death or between multiple factors and death. Urine myoglobin detected by dipstick/ultrafiltration was positive in only 19%. Toxins are the most frequent cause of rhabdomyolysis, but in most cases more than 1 etiologic factor was present. Patients using illicit drugs or on prescribed polytherapy are at risk for rhabdomyolysis. The absence of urine myoglobin, by qualitative assay, does not exclude rhabdomyolysis. With appropriate care, death is rare. Abbreviations: ARF = acute renal failure, CK = creatine kinase, ICU = intensive care unit, NMS = neuroleptic malignant syndrome.

Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting.

PURPOSE To determine the maximum-tolerated doses (MTD), the principal toxicities, and the pharmacologic behavior of high doses of Taxol (paclitaxel; Bristol-Myers Squibb, New York, NY) combined with cisplatin and granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS Untreated and minimally pretreated solid-tumor patients received 24-hour infusions of Taxol on day 1 followed by cisplatin on day 2 and G-CSF, 5 micrograms/kg/d subcutaneously (SC), beginning on day 3. Treatment was repeated every 3 weeks. Starting doses of Taxol and cisplatin were 135 and 75 mg/m2, respectively. RESULTS The development of a severe peripheral neuropathy and/or severe myalgias precluded the chronic administration of Taxol and cisplatin with G-CSF at doses greater than 250 mg/m2 and 75 mg/m2, respectively. At this dose, the mean Taxol steady-state plasma concentration (Css) exceeds concentrations capable of inducing pertinent antimicrotubule effects in vitro. The severity of the neuropathy was related to the cumulative dose of Taxol, the magnitude of the dose administered during each treatment, and the presence of a pre-existing medical disorder associated with peripheral neuropathy. A proximal myopathy of modest severity also was documented. Although severe neutropenia occurred frequently, especially at the MTD, it was rarely associated with fever (8% of courses), and absolute neutrophil counts (ANCs) less than 500/microL never persisted for more than 5 days. Responses were noted in non-small-cell lung cancer (NSCLC) and head and neck, breast, and esophageal cancers. CONCLUSION Taxol and cisplatin doses of 250 mg/m2 and 75 mg/m2, respectively, can be administered repetitively with G-CSF to untreated and minimally pretreated patients. However, these doses are not recommended for patients with pre-existing neuropathies until additional experience in high-risk patients is obtained. Although this Taxol dose is nearly 85% higher than the dose that can be combined with cisplatin in the absence of G-CSF, this high-dose regimen should not be used outside the investigational setting until a dose-response relationship has been demonstrated for Taxol in randomized clinical trials.

Head drop and camptocormia

The spectrum of bent spine disorders Head ptosis (drop) results from weakness of the neck extensor, or increased tone of the flexor muscles. It is characterised by marked anterior curvature or angulation of the cervical spine and is associated with various neuromuscular (table 1) and extrapyramidal disorders.12–15 Camptocormia or the bent spine syndrome was first described in hysterical soldiers in 1915 by the French neurologist Souques.16 Typically there is marked anterior curvature of the thoracolumbar spine. In some patients the spine is angulated forward, the arms propped against the thigh for support. More cases, all among soldiers, were reported during the first and second world wars. These patients responded well to psychotherapy. Recently camptocormia arising as a result of weakness or abnormality in the tone of the paraspinal muscles has been described (table 2). In contrast with other skeletal disorders of the spine such as kyphosis, the deformity in head ptosis and camptocormia is not fixed and is corrected by passive extension or lying in the supine position. It is not possible to straighten the neck or back voluntarily. The evaluation of these disorders can indeed be challenging and often no definite diagnosis is made, as illustrated by four cases of head ptosis and camptocormia seen by us at the Johns Hopkins Hospital. View this table: Table 1 Neuromuscular causes for head ptosis View this table: Table 2 Causes of camptocormia An 80 year old man developed head ptosis insidiously over a period of few weeks. A week before this he had an upper respiratory tract infection and also experienced transient sharp pain over the left and then the right shoulder. He had no diplopia, dysarthria, dysphagia, limb weakness, or fatiguability. Examination showed severe neck extensor weakness, Medical Research Council (MRC) grade 2. Muscle strength was normal in all other cranial, proximal, and distal limb muscles. Serum …

Nerve conduction studies in adrenomyeloneuropathy

OBJECTIVE--Adrenomyeloneuropathy (AMN) is an X linked metabolic disorder presenting with progressive spastic paraparesis in the third to fifth decade of life. Although peripheral neuropathy is also present in most patients, prominent pyramidal signs may make its clinical recognition difficult. The objective was to characterise the peripheral neuropathy in patients with AMN by nerve conduction studies. METHODS--Nerve conduction studies were performed in 99 men known to have AMN and in 38 heterozygous women, all of whom had neurological disabilities. RESULTS--Of the 13 variables obtained, at least one was abnormal in 82% of patients. The abnormalities were more common in men than in women (87% v 67%); in legs than in arms (77% v 38%); in motor than in sensory conduction (80% v 39%); and in latency (distal and F wave) and velocity compared with amplitude (80% v 29%). Twenty six patients had at least one nerve variable value in the demyelinating range. Four variables (sural velocity, peroneal amplitude, peroneal velocity, and peroneal F wave) were correlated with the expanded disability status scale; five variables (peroneal velocity, tibial H reflex, median distal latency, median conduction velocity, and median F wave latency) were correlated with serum very long chain fatty acids (VLCFAs); and two variables (sural amplitude and peroneal distal latency) were more likely to be abnormal in patients with normal adrenal function than in patients with Addisons disease. CONCLUSIONS--Nerve conduction studies in patients with AMN are often abnormal and suggest a mixture of axonal loss and multifocal demyelination. Their correlation with disability status and serum VLCFAs suggests that measures from nerve conduction studies may be useful in evaluating future treatments.

Multifocal motor neuropathy Is conduction block essential

Recognition of new clinical phenotypes requires knowledge and clinical experience together with a new insight, often provided by an unexpected test result. Sometimes, as in multifocal motor neuropathy (MMN), the abnormal test result becomes the gold standard for diagnosis, superceding the clinical phenotype that initially defined the syndrome. MMN has a prevalence of 1 to 2 per 100,000. Despite its rarity, it is important because it is treatable, although not curable. It was initially recognized as a disorder that could be confused with ALS1 but is now well known as a distinct motor neuropathy. Clinically, MMN is characterized by slowly progressive asymmetric distal weakness, generally affecting the upper limbs. Initially, muscle bulk is relatively well preserved, and weakness is in the distribution of one or more peripheral nerves. Sensation is intact, although in 20% there may be patchy distal loss. Tendon reflexes are usually asymmetrically reduced. There are often local fasciculations and cramps, suggesting ALS as a possible diagnosis, but electrodiagnostic testing in MMN, and not in ALS, reveals partial motor conduction block (CB), defined as reduction in proximally stimulated muscle evoked response compared with the distally stimulated response, in one or more nerves at sites away from potential points of nerve compression. Patients with MMN improve …

Worsening of multifocal motor neuropathy during pregnancy

Abstract—Three women with multifocal motor neuropathy (MMN) were treated during pregnancy. Compared with their pregestation strength, the women became weaker in previously involved muscles and showed new weakness in previously unaffected muscles. All were treated with IV immunoglobulin during pregnancy and improved in strength. After pregnancy, strength in all patients returned to the prepregnancy state. The authors conclude that pregnancy may worsen MMN.

Brachial plexopathies: etiology, frequency, and electrodiagnostic localization.

Objectives: Brachial plexopathy is clinically, and electrodiagnostically, a well-recognized entity. However, the involvement pattern of different parts of the plexus with different etiologies has not been well-characterized. Methods: A retrospective analysis of clinical and electrophysiologic findings in 203 patients with brachial plexopathies was performed. Results: Of 203 patients with brachial plexopathy, 182 (90%) were supraclavicular and 21 (10%) were infraclavicular. The following localizations were noted: upper trunk (UT) 27%; lower trunk (LT) 11%; UT + MT (middle trunk) 11%; LT + MT 7%; UT + MT + LT 25%; and UT + LT 1. Among the patients with brachial neuritis, 47% patients did not have pain before the onset and only 28% had a definable antecedent illness. Conclusion: We report the largest to date reported case series of well-characterized brachial plexopathy patients. Upper trunk was the most frequently affected site of injury. In brachial neuritis, absence of pain and antecedent viral illness is more common than described in the literature.

Chronic demyelinating polyneuropathy associated with eosinophilia-myalgia syndrome.

Eosinophilia-myalgia syndrome (EMS) is a newly described syndrome associated with use of L-tryptophan. A neuropathy with features of axonal degeneration has also been described in conjunction with EMS. Demyelinating polyneuropathy is not a well recognised association of the syndrome. The two patients with EMS reported presented with profound weakness and sensory loss and were found to have clinical, electrophysiological and pathological evidence of a chronic demyelinating polyneuropathy. The concurrence of this neuropathy with EMS, as well as several other features of their illness, is suggestive of an immune mediated mechanism in the pathophysiology of EMS.

Reply from the authors [3]

To the Editor: The recently published Practice Advisory was needed, is timely, and is sensible.1 The Therapeutics and Technology Assessment Subcommittee of the AAN found little compelling evidence favoring decompression of leg nerves in diabetic symmetric distal sensorimotor polyneuropathy (DSPN). It should be emphasized that it is decompression of leg nerves at anatomic sites not known to be entrapped that is being discussed (which may not have been sufficiently emphasized in the Advisory) and corrected prevalence figures for DSPN should be provided—the figures provided in the Advisory were for all types of neuropathy (i.e., 66% for type 1 and 59% for type 2 diabetics).1 For DSPN, the estimated prevalence is 54% for type 1 and 45% for type 2 diabetes. The minimal criteria used for the diagnosis of DSPN were two or more abnormalities from among neuropathy symptoms, signs, attributes of nerve conduction, quantitative sensation tests, or heartbeat decrease with deep breathing or Valsalva maneuver (in all cases using standard tests with values corrected for age, gender, and physical variables). When the minimal criterion for DSPN is a composite score of five attributes of nerve conduction of the leg (with values expressed as normal deviates [from percentiles] and with all abnormalities expressed in the upper tail of the normal distribution [summated normal deviates of five attributes of nerve conduction]), the estimated percentages are 55% and 32%. Providing these corrected prevalence values is not meant to detract from the main conclusion of the Advisory.

Perioperative bilateral median neuropathy.

NERVE injuries associated with surgical operations are well recognized and described in literature. 1,2 Ulnar neuropathy, brachial plexus, and lumbosacral roots injuries are the most frequent, as shown by two large reviews on anesthesia-related nerve damage from the American Society of Anesthesiologists closed claims study. 3,4 Several factors such as section, compression, traction, and ischemia, contribute to the nerve injuries but the exact mechanism(s) in an individual case often is unclear. 4,5 We describe a case of perioperative bilateral median neuropathy at the distal forearm, an uncommon site of nerve injury, which we ascribe to demyelinative conduction block secondary to nerve compression.