UNASSIGNED: Spinal cord injury (SCI) presents significant challenges due to its debilitating nature and potential complications. While few medications have shown efficacy in improving neurological recovery, 4-Aminopyridine (4-AP), a voltage-gated potassium channel blocker, has been used clinically off-label to improve neurologic function in adults with spinal cord-related paralysis. However, evidence regarding its safety and effectiveness in the pediatric population remains scarce, as it is approved for use in older patients.
UNASSIGNED: This manuscript reports the case of a pediatric patient who sustained a traumatic cervical SCI. Initial neurological assessment indicated a C1 motor complete SCI. Surgical intervention for bullet removal and spinal fusion was carried out, followed by comprehensive inpatient rehabilitation.
UNASSIGNED: 4-AP was introduced three months post-injury and was well-tolerated without obvious adverse effects. Notably, he exhibited neurological and functional improvement after four months of 4-AP use, though his improvement followed the expected trajectory of recovery. To date, this case represents the first case of 4-AP administration in a pediatric SCI patient, and therefore these findings contribute valuable clinical insight. By documenting the clinical trajectory of this case, this manuscript suggests 4-AP may be safe for use in pediatric patients.

OBJECTIVE: Dalfampridine (DFP) is used to improve motor functions in patients with multiple sclerosis (MS). Overdose of DFP can occur for a variety of reasons and can lead to a state of epilepsy.
METHODS: A 24-year-old woman with MS was admitted to hospital with severe sweating and delirium after attempting suicide by overdosing on DFP. At the time of hospitalization, she developed a tonic-clonic seizure that did not respond to immediate intravenous (IV) diazepam injection, followed by intravenous sodium valproate. Therefore, according to the hospital protocol of the neurology department, the patient was intubated and IV infusion of midazolam was started, Due to the persistence of seizures, sodium thiopental began and the patient was admitted to the intensive care unit (ICU). In the ICU, she received an infusion of sodium thiopental and intravenous sodium valproate, monitored by a daily electroencephalogram (EEG). The patient was discharged after four days due to her stable medical condition.
CONCLUSIONS: Epilepsy in case of overuse of DFP should be considered as a life-threatening side effect and timely treatment should be done to prevent damage to the nervous system.

This case series study aimed to evaluate the safety, feasibility, and positive outcome of the neurorehabilitation multimodal protocol (NRMP) in 16 chronic post-surgical IVDD Hansen type I dogs, with OFS 0/DPP- (n = 9) and OFS 1/DPP+ (n = 7). All were enrolled in the NRMP for a maximum of 90 days and were clinically discharged after achieving ambulation. The NRMP was based on locomotor training, functional electrical stimulation, transcutaneous electrical spinal cord stimulation, and 4-aminopyridine (4-AP) pharmacological management. In the Deep Pain Perception (DPP)+ dogs, 100% recovered ambulation within a mean period of 47 days, reaching OFS ≥11, which suggests that a longer period of time is needed for recovery. At follow-up, all dogs presented a positive evolution with voluntary micturition. Of the DPP- dogs admitted, all achieved a flexion/extension locomotor pattern within 30 days, and after starting the 4-AP, two dogs were discharged at outcome day 45, with 78% obtaining Spinal Reflex Locomotion (SRL) and automatic micturition within a mean period of 62 days. At follow-up, all dogs maintained their neurological status. After the NRMP, ambulatory status was achieved in 88% (14/16) of dogs, without concurrent events. Thus, an NRMP may be an important therapeutic option to reduce the need for euthanasia in the clinical setting.

BACKGROUND: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids.
METHODS: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation.
RESULTS: Five out of 7 patients presented a clinical improvement persisting at last 5-year follow-up; 2 out of them improved taking only 3,4-DAPP at the maximal dosage, whereas the remaining received concomitant medications, such as prednisone and azathioprine. However, the clinical amelioration was not statistically significant. No one of the patients reported severe adverse events, except one, complaining of transient chin and perioral paresthesias. A significant association between QMG and the type of pharmacological drugs therapy (P = .028) emerged. Indeed, we observed an improvement of the clinical condition in all 3 subjects treated with 3,4-DAPP and prednisone.
CONCLUSIONS: In this study, we confirm 3,4-DAPP treatment efficacy on muscle strength, but minor evidence of drug effectiveness have been demonstrated on the autonomic nervous system involvement and on the deep tendon reflexes reappearance, a part from patients who received 3,4-DAPP associated to prednisone.

Apart from infectious causes and cerebellar dysfunction associated with acquired immune deficiency syndrome dementia or HIV-associated neurocognitive disorder, cerebellar dysfunction in HIV-positive individuals has been ascribed to granule cell neuronopathy as well as primary cerebellar atrophy without identifiable etiology. We report the case of a patient with progressive cerebellar dysfunction as the primary manifestation of HIV infection. No symptom improvement was seen under combination antiretroviral therapy, which had been established upon diagnosis, but the patient improved rapidly under 4-aminopyridine treatment, which was recommended 1 year later. Our report, adding to the rather small number of reports of HIV-associated cerebellar atrophy and dysfunction as a primary manifestation of HIV infection, draws attention to HIV as a possible differential etiology of a cerebellar syndrome. Further, rapid improvement of symptom severity under 4-aminopyridine treatment warrants further investigation with longer-term follow-up into the effectiveness of this compound in gait disorder associated with HIV infection.

BACKGROUND: Lambert-Eaton myasthenic syndrome is a rare autoimmune disorder of neuromuscular transmission due to the presence of antibodies to presynaptic P/Q-type voltage-gated calcium channels. The gold standard of therapy is the potassium channel blocker 3,4-diaminopyridine. To the best of our knowledge, no clinical reports have been published to date about long-term follow-up outcomes in patients who discontinued 3,4-diaminopyridine therapy. In addition, we know of no recent articles in which the natural history in patients with autoimmune-mediated Lambert-Eaton myasthenic syndrome has been addressed. In this report, we describe the cases of two such patients.
METHODS: Patient 1 was a Caucasian man who had been diagnosed at age 15 years with Lambert-Eaton myasthenic syndrome with symptoms of fluctuating muscle weakness and easy fatigability. These symptoms stabilized, and his electrophysiological parameters normalized, during treatment with a maintenance dose of 50mg/day of 3,4-diaminopyridine. After 5.5 years, however, he wished to discontinue the treatment. After that point, his electrophysiological parameters and presynaptic P/Q-type voltage-gated calcium-channel antibody titer remained stable. During the 15-year follow-up period, patient 1 reported mild exertion-induced complaints but did not feel restricted in his occupation and most daily activities. Patient 2 was a Caucasian man diagnosed at 32 years of age with a moderate limb girdle syndrome. He was treated with up to 80 mg/day of 3,4-diaminopyridine. Because of the drug\'s very short-lasting effect (<1 hour), however, he took it mostly irregularly (≤ 1 × 20 mg/day). During the 14- year period of observation, his repetitive nerve stimulation responses and presynaptic P/Q-type voltage-gated calcium-channel antibody titer remained stable, his compound muscle action potential amplitudes were decreasing and his clinical symptoms did not deteriorate. At his last follow-up examination, patient 2 was independent in all of his daily activities.
CONCLUSIONS: Some patients with autoimmune-mediated Lambert-Eaton myasthenic syndrome show a stable clinical long-term course without treatment. The benefit of each long-term therapy should be critically assessed during follow-up, and possible side effects should be balanced against the quality of life in these patients.

The reversible potassium channel blocker 4-aminopyridine is effective in the treatment of numerous cerebellar dysfunctions, such as episodic ataxia type 2 and downbeat nystagmus syndrome. In 2011, its sustained release form, dalfampridine, was admitted in Europe for the treatment of walking difficulties in patients with multiple sclerosis (MS). Here we report the case of a 44-year old patient with a progressive MS whose upper limb tremor was markedly reduced under treatment with 4-aminopyridine, as documented in a Tremor Activities of Daily Living questionnaire and in the 9-Hole Peg test. Hand accelerations decreased in the left hand from 10.9 m/sec(2) to 2.2 m/sec(2) and in the right hand from 4.2 m/sec(2) to 0.9 m/sec(2). This case report indicates for the first time that 4-aminopyridine might be effective in the symptomatic treatment of tremor entities in patients with MS. The finding calls for further prospective studies to determine the usefulness of 4-aminopyridine or its sustained-release form dalfampridine in treating patients with tremor and MS.

BACKGROUND: 4-Aminopyridine (4-AP) selectively blocks voltage-gated potassium channels, prolongs the action potential, increases calcium influx, and subsequently, enhances interneuronal and neuromuscular synaptic transmission. This medication has been studied and used in many disease processes hallmarked by poor neuronal transmission in both the central and peripheral nervous systems including: multiple sclerosis (MS), spinal cord injuries (SCI), botulism, Lambert-Eaton syndrome, and myasthenia gravis. It has also been postulated as a potential treatment of verapamil toxicity and reversal agent for anesthesia-induced neuromuscular blockade. To date, there have been limited reports of either intentional or accidental 4-AP toxicity in humans. Both a case of a patient with 4-AP toxicity and review of the literature are discussed, highlighting commonalities observed in overdose.
METHODS: A 37-year-old man with progressive MS presented with diaphoresis, delirium, agitation, and choreathetoid movements after a presumed 4-AP overdose. 4-AP concentration at 6 h was 140 ng/mL. With aggressive benzodiazepine administration and intubation, he recovered uneventfully.
CONCLUSIONS: The commonalities associated with 4-AP toxicity conforms to what is known about its mechanism of action combining cholinergic features including diaphoresis, altered mental status, and seizures with dopamine-related movement abnormalities including tremor, choreoathetosis, and dystonia. Management of patients poisoned by 4-AP centers around good supportive care with definitive airway management and controlling CNS hyperexcitability aggressively with gamma-aminobutyric acid agonist agents. Adjunctive use of dopamine antagonists for extrapyramidal effects after sedation is a treatment possibility. As 4-aminopyridine recently received Federal Drug Administration approval for the treatment of ambulation in patients with MS, physicians should be keenly aware of its presentation, mechanism of action, and management in overdose.

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A four-year-old neutered male bichon frise was presented for the evaluation of chronic, progressive yet episodic neurological dysfunction that was predominantly cerebellar in nature. Diagnostic testing including haematology, serum chemistry, magnetic resonance imaging, cerebrospinal fluid analysis and urine organic acid screening was normal. Trial therapies with phenobarbital, prednisone and acetazolamide were unsuccessful. Treatment with 4-aminopyridine led to complete resolution of the signs.