The first line treatments for fatigue are usually nonpharmacologic interventions, such as routine exercise. If symptoms persist, treatment with modafinil [1-6] or amantadine can be considered, although they are not approved by the FDA for MS-associated fatigue. Several recent RCTs showed a beneficial effect of Methylphenidate, a dopamine agonist which inhibitis presynaptic dopamine transporters leading to suppression of dopamine reuptake [7,8], in reducing fatigue in Parkinson’s patients , in patients with chronic fatigue syndrome  and in cancer patients.  Controlled studies in PedMS patients with methylphenidate have not been conducted.
Lower urinary tract dysfunction
Lower urinary tract dysfunction (LUT) is common in MS patients and is one of the major factors impacting their quality of life. The overall incidence in PedMS has not been well documented, however does occur particularly in patients with spinal cord lesions. Antimuscarinics are considered as first-line treatments, but if they are ineffective, or poorly tolerated, other approaches, such as intradetrusor botulinum toxin A injections, tibial nerve stimulation and sacral neuromodulation may be considered. Surgical procedures should be performed only if conservative measures have failed. PedMS patients with severe LUT symptoms require multidisciplinary approach (i.e. pediatric urologist) and long-term follow-up monitoring. 
For generalized spasticity, treatments with diazepam or baclofen or tizanidine may be used in PedMS as in pediatric patients with cerebral palsy. Baclofen is generally well tolerated in adult MS, but, since abrupt discontinuation can result in seizures, hallucinations, and hyperthermia, [13,14] caution should be considered when used in children. For focal spasticity, botulinum toxin A is recommended.
Neuropathic pain is frequently reported in adult MS. Gabapentin is the most commonly used treatment in adult MS. A significant pain relief, at a dose of 600 mg per day, was demonstrated in one study . Side effects included mental cloudiness, somnolence, and gastrointestinal complaints. Gabapentin has not been studied in PedMS.
- MacAllister, W.S., et al., Fatigue and quality of life in pediatric multiple sclerosis. Mult Scler, 2009. 15(12): p. 1502-8.
- Goretti, B., et al., Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis. Mult Scler, 2012. 18(3): p. 329-34.
- Parrish, J.B., et al., Fatigue and depression in children with demyelinating disorders. J Child Neurol, 2013. 28(6): p. 713-8.
- Zifko, U.A., et al., Modafinil in treatment of fatigue in multiple sclerosis. Results of an open-label study. J Neurol, 2002. 249(8): p. 983-7.
- Rammohan, K.W. and D.J. Lynn, Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology, 2005. 65(12): p. 1995-7; author reply 1995-7.
- Stankoff, B., et al., Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology, 2005. 64(7): p. 1139-43.
- Volkow, N.D., et al., Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci, 2001. 21(2): p. RC121.
- Prommer, E., Methylphenidate: established and expanding roles in symptom management. Am J Hosp Palliat Care, 2012. 29(6): p. 483-90.
- Mendonca, D.A., K. Menezes, and M.S. Jog, Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial. Mov Disord, 2007. 22(14): p. 2070-6.
- Blockmans, D., et al., Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med, 2006. 119(2): p. 167 e23-30.
- Roth, A.J., et al., Methylphenidate for fatigue in ambulatory men with prostate cancer. Cancer, 2010. 116(21): p. 5102-10.
- Phe, V., E. Chartier-Kastler, and J.N. Panicker, Management of neurogenic bladder in patients with multiple sclerosis. Nat Rev Urol, 2016.
- Hyser, C.L. and M.E. Drake, Jr., Status epilepticus after baclofen withdrawal. J Natl Med Assoc, 1984. 76(5): p. 533, 537-8.
- Malhotra, T. and I. Rosenzweig, Baclofen withdrawal causes psychosis in otherwise unclouded consciousness. J Neuropsychiatry Clin Neurosci, 2009. 21(4): p. 476.
- Houtchens, M.K., et al., Open label gabapentin treatment for pain in multiple sclerosis. Mult Scler, 1997. 3(4): p. 250-3.