Michael J. Giuliani

Causes of neuromuscular weakness in the intensive care unit : A study of ninety-two patients

The spectrum of neuromuscular disorders among intensive care unit (ICU) patients has shifted toward disorders acquired within the ICU and away from “traditional” neuromuscular disorders that lead to ICU admission. We sought to assess this spectrum by determining the causes and relative frequencies of neuromuscular disorders that led to electromyography (EMG) examinations in our ICU population. Ninety‐two patients were studied over a 4½‐year period. Twenty‐six (28%) had neuromuscular disorders (mainly Guillain–Barré syndrome, myopathy, and motor neuron disease) that led to ICU admission. Among patients who developed weakness in the ICU, there was a predominance of organ transplant patients and patients with the systemic inflammatory response syndrome and multiorgan dysfunction. Thirty‐nine (42%) developed acute myopathy (consistent with critical illness myopathy in most), and 13% developed acute axonal sensorimotor polyneuropathy (mainly critical illness polyneuropathy). Patients with acute myopathy and acute axonal sensorimotor polyneuropathy had similar functional outcomes. We conclude that among patients who underwent EMG in our ICU population, acute myopathy is three times as common as acute axonal polyneuropathy, and the outcomes from acute myopathy and acute axonal polyneuropathy may be similar.

Acute myopathy after liver transplantation

Acute myopathy is a cause of weakness and additional morbidity in a variety of critically ill patients, including transplant recipients. We report the incidence of and risk factors associated with acute myopathy after orthotopic liver transplantation (OLTx). One hundred consecutive adult patients were prospectively assessed for muscle weakness after OLTx. Electrodiagnostic studies and muscle biopsies were performed on consenting affected patients. Potential risk factors for myopathy were evaluated in patients with myopathy versus control subjects. Seven patients developed acute persistent weakness after OLTx. Electrodiagnostic studies were consistent with a necrotizing myopathy. Histopathologic evaluation in five revealed a necrotizing myopathy with loss of myosin thick filaments. A higher initial index of illness severity, dialysis requirement, and higher doses of glucocorticoids were associated with development of myopathy. Patients with myopathy subsequently remained in the intensive care unit (ICU) longer than unaffected patients. In conclusion, acute substantial weakness was a source of additional morbidity in 7% of patients after OLTx. Most had myopathy with loss of myosin thick filaments. Patients with greater severity of illnesses and renal failure requiring dialysis were more likely to be affected. The effect of reducing exposure to corticosteroids in high-risk patients warrants further investigation.

Comparison of different modalities for detection of small fiber neuropathy

OBJECTIVES In general, large fiber sensory function is easier to assess than small fiber function both clinically and electrophysiologically. Therefore, small fiber sensory neuropathies are more difficult to diagnose. The relative sensitivities of different electrodiagnostic tests for small fiber neuropathy are not known. We sought to determine and compare the sensitivities of quantitative thermal sensory testing (QST), quantitative sudomotor axon reflex testing (QSART), and cardiovascular autonomic testing for diagnosis in patients with clinically suspected small fiber neuropathy. METHODS 15 adult patients with clinically suspected small fiber sensory neuropathy underwent neurologic examination, QST, and QSART. Twelve also underwent cardiovascular autonomic testing. RESULTS 80% had an abnormal neurologic examination consistent with small fiber neuropathy, while 93% had at least one abnormal quantitative test. QSART was most sensitive with 12 of 15 (80%) having abnormal studies while 10 of 15 (67%) had abnormal thermal thresholds by QST. Abnormal heart rate with deep breathing was detected in 9 of 12 (75%) patients. CONCLUSION Of the modalities tested, QSART was most sensitive in confirming the clinical suspicion of a small fiber neuropathy. Autonomic cardiovascular abnormalities were also common in our patients. Clinical examination and QSART may be optimal for screening patients for small fiber neuropathy.

Neuromyotonia: autoimmune pathogenesis and response to immune modulating therapy

BACKGROUND Neuromyotonia (NMT) has been postulated to be an autoimmune channelopathy, probably by affecting voltage gated potassium channels (VGKC) leading to excitation and abnormal discharges [Sinha et al., Lancet 338 (1991) 75]. OBJECTIVE To report three patients with NMT who had other associated immune-mediated conditions, i.e., myasthenia gravis, thymoma and various types of peripheral neuropathies. One patient had peripheral neuropathy and involvement of pre- and post-synaptic neuromuscular junction. RESULTS All three patients had evidence of polyneuropathy and neuromyotonic discharges on electrodiagnostic studies. Elevated acetylcholine receptor antibodies were noted in all patients and malignant thymoma was found in two patients with metastasis. All three patients showed moderate to marked response to plasma exchange. CONCLUSIONS These findings strongly suggest a humoral autoimmune pathogenesis of NMT, probably by K(+) channel involvement, affecting acetylcholine quantal release and postsynaptic membrane. Clinicians should be aware of this association of immune-mediated conditions in NMT patients and marked improvement with plasma exchange.

Acute onset of colchicine myoneuropathy in cardiac transplant recipients: case studies of three patients

Colchicine causes both muscle and peripheral nerve toxicity of subacute onset in patients with renal insufficiency. We report three cardiac transplant recipients, treated with colchicine for cyclosporin A (CyA)-induced gout, who developed acute weakness due to colchicine myoneuropathy. The onset of disabling weakness occurred over a 1-2 week period. All three patients had concomitant renal insufficiency and an elevated serum creatine kinase and two elevated CyA levels at the time of presentation. Electromyography revealed features of myopathy and motor axonal neuropathy in all three patients. Two underwent muscle biopsy which confirmed the presence of sarcoplasmic vacuoles characteristic of colchicine-induced myopathy. All patients rapidly improved with either colchicine dose reduction or drug discontinuation. In conclusion, cardiac transplant recipients treated with CyA and colchicine may be at increased risk of developing colchicine-induced myoneuropathy especially in the setting of concurrent renal insufficiency. In patients with post-transplantation gouty arthritis, other treatment modalities are suggested; and if colchicine is administered, the dose should be reduced, CyA levels should be monitored closely and patients should be assessed for signs of neuromuscular toxicity.

Hepatic myelopathy Case report with review of the literature

Hepatic myelopathy is a rare complication of hepatic insufficiency, causing progressive spastic paraparesis. There are few reports detailing the clinical and diagnostic aspects of this uncommon cause of neurological deterioration in patients with liver disease. Early recognition of this disorder will become more important as patients with liver disease survive longer due to medical advances, including liver transplantation. We present an additional patient with hepatic myelopathy associated with infantile portal vein thrombosis and review the previous reports of hepatic myelopathy in the English literature.

Cerebrovascular Disease in Women

Cerebrovascular disease is one of the leading causes of death in women in the United States. Pregnancy and hormonal therapy have been associated with an increased risk of stroke in young women. Other conditions, more common in women, such as migraine headaches, rheumatologic disorders and antiphospholipid antibodies predispose women to cerebral ischemia. Women may also respond differently to antiplatelet therapy. The identification and treatment of such conditions will improve outcome in women with stroke and may prevent recurrent cerebrovascular events.

Fluctuating clinical myotonia and weakness from Thomsen’s disease occurring only during pregnancies ☆

Advances in molecular genetics are allowing better phenotype to genotype correlation of the non-dystrophic myotonic disorders. We report a 32-year-old woman, who first noted myotonia that was associated with weakness during her first pregnancy. The work-up disclosed that she had Thomsens disease which is not known to be associated with weakness. In addition, her myotonia was of the fluctuating type and occurred (symptomatically) only during two pregnancies. We discuss the evaluation of myotonia in the pregnant woman which led to the diagnosis of Thomsens disease and we conclude that in exceptional cases, fluctuating myotonia and weakness occurs in autosomal dominant chloride channel myotonia (Thomsens disease).

Tolerability of recombinant-methionyl human neurotrophin-3 (r-metHuNT3) in healthy subjects

This phase I, double‐blind, randomized, placebo‐controlled study evaluated the safety of single and multiple (daily for 7 days) subcutaneous administrations of recombinant–methionyl human neurotrophin‐3 (r‐metHuNT3) in healthy human volunteers at seven doses, ranging from 3 to 500 μg/kg/day. No serious or life‐threatening adverse events occurred. The most frequently recorded adverse effects were mild injection‐site pain, diarrhea, and elevation of liver function tests. No change in neurologic function was noted with these dosing regimens. We conclude that r‐metHuNT3 is safe and well tolerated in the dosages used in this study.

Mononeuropathies associated with liver transplantation

Mononeuropathies associated with orthotopic liver transplantation were evaluated in a prospective manner. Ten percent of liver transplant recipients were noted to have focal peripheral nerve lesions in the postoperative period. The ulnar nerve was most commonly involved, with intraoperative compression or postoperative trauma as possible mechanisms of injury. Other upper extremity mononeuropathies were likely a result of vascular cannulations. No brachial plexus injuries occurred. Diabetes and alcoholism were not risk factors for the development of a mononeuropathy.