Obinutuzumab, a new anti-CD20 antibody, and chlorambucil are active and effective in anti-myelin-associated glycoprotein antibody polyneuropathy.

BACKGROUND AND PURPOSE: Rituximab, a chimeric anti-CD20 monoclonal antibody, has been used in polyneuropathy associated with anti-myelin-associated glycoprotein (anti-MAG) antibody polyneuropathy with controversial results. Herein, two patients with anti-MAG antibody neuropathy and concurrent chronic lymphocytic leukemia (CLL) are reported, who dramatically responded to obinutuzumab, a novel glycoengineered humanized anti-CD20 monoclonal antibody. METHODS: Patient 1 was an 82-year-old man with severe demyelinating sensory-motor neuropathy. He was wheelchair-bound, with loss of sensation up to the knees. He had a CLL, immunoglobulin M (IgM) lambda monoclonal gammopathy, with anti-MAG antibodies >70 000 Bühlmann titer units (BTU). Patient 2 was an 84-year-old woman with demyelinating neuropathy, paresthesias and gait instability. She had CLL and IgM kappa paraprotein with anti-MAG antibodies >70 000 BTU. Both patients were treated with obinutuzumab intravenously at 100 mg on day +1, 900 mg +2, then at 1000 mg on days 8 and 15 of cycle 1 and day 1 of cycles 2-6; chlorambucil was given orally at 0.5 mg/kg on days 1 and 15 of cycles 1-6. RESULTS: Patient 1 at cycle 6 was able to stand, gait was possible with monolateral support, hypoesthesia and strength improved. M-protein and IgM level decreased. In patient 2, already after three cycles, the monoclonal component disappeared and there was dramatic improvement of symptoms and gait normalization. At the end of therapy anti-MAG antibody titer decreased to 5462 BTU. Neurophysiology also improved. CONCLUSIONS: In our patients, obinutuzumab was effective as a first-line treatment of anti-MAG antibody polyneuropathy. CLL might have had a role in the response to therapy, but the associations might be considered in future trials.

Observational multicentric survey on carpal tunnel syndrome: demographic and clinical data from 34 Italian centers.

OBJECTIVE: To evaluate the current management of carpal tunnel syndrome (CTS) at a national level. PATIENTS AND METHODS: A multicentric observational study was conducted in 34 Italian centers by specialists participating in the Management of Peripheral Neuropathies Study Group on 377 patients (age, mean±SD 56±14.4 years, 73.2% females) with CTS. The characteristics of the disease and its management were recorded at baseline and during a 2-month follow-up using a standardized clinical record and assessed with validated clinical tests. RESULTS: A wide variability in the interventions prescribed and classified according to three categories (physical, pharmacological and neurotrophic therapies) was evident. A subgroup of 303 patients was treated with a combination of neurotrophic agents containing alpha-lipoic acid (ALA). At the end of the follow-up, a general improvement in symptoms and functional impairment was observed, with a significant reduction in BCTQ (Boston Carpal Tunnel Questionnaire) (p<0.001) and in NRS (Pain Numeric Rating Scale, p<0.001 for both nocturnal and diurnal pain). CONCLUSIONS: An appropriate approach to CTS implies a multimodal and multidisciplinary management, involving several specialists and using a variety of conservative interventions. Conservative (physical and pharmacological) interventions can provide a clinical improvement in patients with CTS.

Ultrasound assessment of oxaliplatin-induced neuropathy and correlations with neurophysiologic findings.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy is a major adverse effect of oxaliplatin (OXL) treatment. Whereas neurophysiologic study is commonly used to assess the occurrence and severity of polyneuropathies, ultrasound (US) analysis of the peripheral nerves, an emerging technique in the study of peripheral nerve diseases, has never been used in chemotherapy-induced peripheral neuropathy. PATIENTS AND METHODS: Fifteen patients (four women; 11 men; mean age, 60.1 ± 10.6 years; median, 62; range, 37-75) with colorectal cancer treated with OXL-based treatment have been clinically and neurophysiologically evaluated before and after OXL therapy. At the end of chemotherapy, all patients underwent also nerve US study at four limbs, and the findings correlated with clinical and neurophysiologic measures. RESULTS: Clinical and neurophysiological evaluation showed that 13 of 15 (86.7%) patients developed sensory axonal neuropathy, 10 of whom severe (two or more sensory nerve action potential amplitude absent and the other amplitudes decreased of ≥50%). Nerve US did not reveal decreased cross-sectional area (CSA), a reported finding in axonal neuropathies. Instead increased CSA at entrapment sites (median nerve at wrist and ulnar nerve at elbow) was found in 09/15 (60%) of patients. DISCUSSION: Sensory axonal neuropathy is a very common complication of OXL therapy, affecting almost 90% of patients. US findings of enlargement of median and ulnar nerves, mostly at entrapment sites, in patients with no history or symptoms of neuropathies at recruitment, and no neurophysiologic evidence of entrapment, may be expression of increased, OXL-induced, nerve susceptibility to mechanical damage. An ongoing prospective study will help clarify these findings.

Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients.

BACKGROUND: To report our prospective experience on the incidence and pattern of oxaliplatin (OXA)-induced peripheral neuropathy (OXA-IPN) in patients with colorectal cancer (CRC) treated with either FOLFOX-4 or XELoda + OXaliplatin (XELOX). PATIENTS AND METHODS: One hundred and fifty patients scheduled to be treated with either FOLFOX or XELOX for CRC were prospectively monitored at baseline and followed-up during chemotherapy. The incidence and severity of symptoms secondary to OXA-IPN were recorded using three different types of assessment, i.e. the motor and neurosensory National Cancer Institute common toxicity criteria, version 3.0 (NCI-CTCv3), the clinical version of the total neuropathy score (TNSc) and electrophysiological scores. RESULTS: Patients treated with either FOLFOX-4 or XELOX manifested similar incidence rates and severities of acute OXA-IPN. However, FOLFOX-4 was associated with increased incidence of chronic neurotoxicity, compared with XELOX-treated patients (n = 64/77 versus 44/73; P = 0.002), at a very similar OXA median cumulative dose during both regimens. Both the NCI-CTCv3 and TNSc demonstrated that the severity of cumulative OXA-IPN in FOLFOX-4-treated patients is higher than in those treated with XELOX. CONCLUSION: The incidence of acute neurotoxicity during FOLFOX-4 therapy is similar to XELOX. However, it seems that FOLFOX-4 is more neurotoxic than XELOX in terms of cumulative OXA-IPN, despite comparable OXA cumulative dose.

Femoral nerve damage after abdominal rectopexy.

Iatrogenic femoral nerve damage has already been described after hysterectomy, but never after abdominal rectopexy. We report the occurrence of femoral nerve injury in six of twenty-four patients operated on for complete rectal prolapse (n = 21) or rectorectal intussusception (n = 3). Four patients had unilateral and two bilateral lesions. All six patients had clinical and electromyographic (EMG) assessment. EMG findings were given a score from 0 (complete denervation) to 5 (normal findings). During the immediate postoperative period all patients complained of reduced cutaneous sensation of the anterior surface of the thigh and knee, and quadriceps weakness. EMG showed complete denervation in one patient, marked denervation in three, and slight or moderate denervation in the remaining two. In five patients there was complete clinical resolution at 3 to 12 months postoperatively, while one showed an improvement only. EMG control performed in four patients showed a full recovery in three. Two patients refused this examination. We believe femoral nerve damage was caused by the large-bladed self-retaining retractors used, which directly or indirectly compressed the femoral nerve.

Posterior interosseous nerve neuropathy. Clinical and electromyographical aspects.

A clinical-EMGraphic examination was carried out in 37 patients with posterior interosseous nerve neuropathy: 5 cases had a traumatic origin, 4 iatrogenic, and 28 non-traumatic. One of the non-traumatic cases had a lipoma, and another had chondroma. In the other cases, nerve entrapment at the level of the arcade of Frohse could be presumed. Acute or chronic onset of the deficit was probably due to repeated pronation-supination hand movements. A motor deficit in finger extension together with a radial deviation of the wrist, was typical. Surprisingly about 50% of the non-traumatic cases showed some sensory disturbance at the forearm, wrist or hand. EMG examination was useful to establish the entity and topography of the deficit. Follow-up was carried out in 27 cases (3 traumatic, 2 iatrogenic and 22 non-traumatic). Even if spontaneous recovery is possible, though infrequent, in non-traumatic cases with marked deficit surgery gave the most satisfactory results, especially when onset had been acute and operation was performed within nine months of onset.