Nakajima M

Results of Quinacrine Administration to Patients with Creutzfeldt-Jakob Disease

Several chemicals inhibit the accumulation of abnormal prion proteins in vitro. We administered one, the antimalarial agent quinacrine, to three patients with sporadic Creutzfeldt-Jakob disease (CJD) and to one with iatrogenic CJD. Quinacrine at 300 mg/day was given enterally for 3 months. Within 2 weeks of administration, the arousal level of the patient with akinetic mutism improved. The other 3 patients, insensible before treatment, had integrative responses such as eye contact or voluntary movement in response to verbal and/or visual stimuli restored. Clinical improvement was transient, lasting 1–2 months during treatment. Quinacrine was well tolerated, except for liver dysfunction and yellowish pigmentation. Although its antiprion activity in the human brain has yet to be proved, these modest effects of quinacrine suggest the possibility of using chemical intervention against prion diseases.

Special sensory ataxia in Miller Fisher syndrome detected by postural body sway analysis

To investigate whether ataxia in Miller Fisher syndrome (MFS) is caused by loss of proprioception or cerebellar dysfunction, we studied the power spectrum peak of the body sway frequency in 10 MFS patients, and compared the results with those of patients with cerebellar or sensory ataxia. The cerebellar patients had a peak at 2.4 Hz, whereas sensory ataxia patients had a 1‐Hz peak. Nine of the MFS patients had a distinct 1‐Hz peak. Clinical sensory loss or abnormal sensory nerve potentials were present in only 3 patients, whereas soleus H‐reflexes were absent in all the MFS patients. MFS patients have dysfunction of the proprioceptive afferent system, and the special sensory ataxia may be caused by the selective involvement of muscle spindle afferents. Ann Neurol 1999;45:533–536

Magnetic resonance imaging at the demyelinative foci in chronic inflammatory demyelinating polyneuropathy

Using MRI, we investigated the morphology and blood-nerve barrier function of the peripheral nerve trunk in 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Eight patients had a focal demyelinative segment in the median or ulnar nerve trunk that was defined by conduction block or abnormal temporal dispersion over a short distance. These demyelinative foci showed nerve enlargement with high signal intensity on proton or T2-weighted images. In four patients with progressive illness or relapse, the enlarged segment showed gadolinium enhancement that disappeared during remission induced by immune therapies. The other four were in the steady phase and showed no gadolinium enhancement of the enlarged nerves. The two patients who showed conduction slowing, but no focal demyelinative focus, had neither nerve enlargement nor gadolinium enhancement. In CIDP, focal conduction abnormalities correlate well with anatomic changes that suggest intermittent, repeated inflammation associated with the breakdown of the blood-nerve barrier.

D-Penicillamine treatment for chronic sensory ataxic neuropathy associated with Sjögren's syndrome

Beneficial treatment has not been established for chronic sensory ataxic neuropathy associated with Sjögrens syndrome (CSAN-SS). We describe two patients with CSAN-SS who clinically improved in response to D-penicillamine treatment. Their neuropathic symptoms were lessened after D-penicillamine, and the results of electrophysiologic studies support the clinical improvement. D-Penicillamine can be considered a potentially beneficial agent in the treatment of CSAN-SS.

Demyelinating polyneuropathy with preferentially-proximal involvement

A 47-year-old man showed progressive, symmetrical weakness in the limbs for 6 months. There was muscle atrophy, fasciculations, and acute denervation without motor conduction abnormalities below the elbows or knees, and motor neuron disease had once been suspected. However, compound muscle action potentials (CMAPs) after proximal stimulation showed an amplitude reduction between axilla and Erbs point for the median and ulnar nerves on both sides. His weakness as well as the amplitude reduction improved after administration of prednisolone. Demyelinative conduction abnormalities can be limited to the proximal segments for at least several months in a conduction equivalent to chronic inflammatory demyelinating polyneuropathy (CIDP).

Demyelinating brachial neuropathy complicating syngeneic graft-versus-host disease.

Autologous bone marrow or peripheral blood stem cell transplantation (PBSCT) has become an important option for patients with leukemia or lymphoma, but tumor recurrence is higher than with allogeneic transplantation. After the autologous transplantation, cyclosporin A (CyA) is used to induce graft-versus-host disease (GVHD) that potentially has graft-versus-leukemic cell reactions. [1,2] We report a patient with multifocal demyelinating neuropathy that appeared with syngeneic GVHD induced by CyA. A 20-year-old asthmatic man presented with a mediastinal tumor associated with superior vena cava syndrome and was diagnosed with non-Hodgkin lymphoblastic lymphoma. He received standard MACOP-B (methotrexate 640 mg IV x3, doxorubicin 80 mg IV x6, cyclophosphamide 550 mg IV x6, vincristine 2.25 mg IV x6, prednisolone 75 mg po daily, and bleomycin 16U IV x3 in 12 weeks), which resulted in a complete remission. After conditioning therapy with busulfan (240 mg po for 4 days) and etoposide (1,500 mg IV for 2 days), he was transplanted with his own peripheral blood stem cells that had been mobilized using granulocyte colony-stimulating factor (G-CSF). The patient received oral CyA 50 mg/d, starting on day 7 after PBSCT, for 3 weeks. A few days after withdrawal of CyA, he developed tingling in the finger tips …

Increased CSF C4d in demyelinating neuropathy indicates the radicular involvement

Plasma and cerebrospinal fluid (CSF) levels of C4d and the circulating immune complex (CIC) to Clq were measured in 12 patients with chronic inflammatory demyelinating polyneuropathy and Guillain‐Barré syndrome. CSF C4d values more than 2 SD from the mean of 8 cervical spongylosis cases were demonstrated in the patients with proximal demyelination. The CSF C4d probably originated from both intrathecal synthesis and the systemic circulation. CSF levels of C4d may serve as a sensitive indicator for the radicular involvement in demyelinating polyneuropathy.