Patient case (clinical description): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient's own account: I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Clinical trial: Use of Dalfampridine in Primary Lateral Sclerosis

Eligibility criteria:
Inclusion Criteria:

          1. Male or female, aged 18-99;

          2. Diagnosis of upper motor neuron disease, compatible with PLS but may include upper
             motor neuron (UMN) predominant ALS, defined as only upper motor neuron (UMN) features
             in at least 2 body regions on examination.

          3. EMG within 3 months of enrollment with minimal or no evidence of lower motor neuron
             disease,

          4. Time from symptom onset > 18 months

          5. No previous allergy to dalfampridine

          6. No current or exposure to any therapeutic agent targeting PLS or ALS within 30 days of
             enrollment.

          7. Must have a forced vital capacity (FVC) ≥ 60% of expected

          8. Written informed consent prior to screening is present.

          9. Subjects on a stable dose of or have not taken Riluzole for at least thirty days

         10. Impaired walking as measured by a Hauser Index of greater than 1 and less than 7 (2 to
             6, inclusive);

         11. Mini Mental Status Score > 22 and deemed by the PI of being capable of providing
             informed consent and following trial procedures.

         12. Geographically accessible to the site.

         13. Women must not be able to become pregnant (e.g., post-menopausal, surgically sterile,
             or using adequate birth control methods) for the duration of the study and three
             months after study completion. Adequate contraception includes: abstinence, hormonal
             contraception (oral contraception, implanted contraception, injected contraception or
             other hormonal contraception, for example patch or contraceptive ring), intrauterine
             device (IUD) in place for ≥ 3 months, barrier method in conjunction with spermicide,
             or another adequate method.

        Exclusion Criteria:

          1. History of clinically significant liver disease, renal disease, peripheral neuropathy,
             serious peripheral vascular disease, known HSP or + C9orf72 or SPG4 mutation, or any
             other medical condition felt to be exclusionary by the investigator;

          2. Unwillingness to sign informed consent or any other reasons for which the investigator
             feels the subject cannot complete the study;

          3. Women who are pregnant, breastfeeding, or trying to become pregnant;

          4. Active cancer within the previous 2 years, except treated basal cell carcinoma of the
             skin;

          5. Subjects taking any other experimental drugs within 30 days prior to enrollment;

          6. Patient has any history of seizures; brain surgery, brain implants, any metallic
             implants above the neck, cardiac pacemakers, cochlear implants, piercing or body
             modification above the neck, known history of TMS related complications or
             side-effects, tinnitus.

          7. Patient has moderate or severe renal impairment as defined by a calculated creatinine
             clearance of ≤50 mL/minute;

          8. Patient has been administered botulinum toxin in the lower extremities within 6 months
             prior to the screening visit and/or is expected to receive botulinum toxin in the
             lower extremities during the course of the study;

          9. Patient has a known allergy to pyridine-containing substances or any of the inactive
             ingredients of the dalfampridine tablet (colloidal silicon dioxide, hydroxypropyl
             methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol,
             and titanium dioxide);

         10. Patient has a history of drug or alcohol abuse within the past year;

         11. Patient has clinically significant abnormal laboratory values.

         12. Anything else that, in the opinion of the SI, would place the subject at increased
             risk or preclude the subject's full compliance with or completion of the study.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 99 Years

Eligibility (NLI label): Contradiction