Table 2.

Summary of screening and treatment recommendations

Domain	Diagnosis	Treatment and surveillance
Genetics	Consider MSP genetic testing in patients with personal or family history of one or more of the described phenotypes including myopathy, PDB, FTD, ALS, CMT, and/or spastic paraplegia Genetic testing is the gold standard for diagnosis of VCP MSP and other genetic causes of MSP Single-gene testing is recommended for patients who have a known familial mutation Multi-gene panel testing is recommended for undifferentiated patients	Confirm VCP inclusion in multi-gene testing panel Genetic counseling
Myopathy	CK can be normal to mildly elevated NCS/EMG can show mixed neurogenic and myopathic features and may help with diagnosis of concomitant neuropathy or motor neuron disease Muscle MRI T1 weight imaging can show “fat pockets” in proximal and distal lower limb muscles Muscle biopsy may show rimmed vacuoles, fiber size variability, ubiquitin and TDP-43 inclusions. It may be helpful in cases of diagnostic uncertainty for other diseases	No disease modifying therapy Supportive management: PT, OT, SLP, RT, mechanical aids PT guidance on appropriate and safe exercise Surveillance: Follow with a multidisciplinary team for standardized strength and functional testing using appropriate COA every 6 months to 1 year, or more frequently if weakness progresses more rapidly
Frontotemporal dementia	Screen for FTD with clinical assessment for behavioral and cognitive impairment, and bedside cognitive tools like MoCA and NPI-Q Formal neuropsychiatric testing if FTD is suspected Brain MRI with atrophy of frontal and/or temporal lobes can support diagnosis FDG PET can show hypometabolism of frontal and/or temporal lobes but is not required for diagnosis	No disease modifying therapy Supportive management: avoiding triggers for high-risk behaviors, caregiver support and education Speech language pathology Anti-depressants and anti-psychotics may have some benefit for the treatment of FTD associated behaviors Surveillance: Annual neuro assessment with bedside tools like MoCA and NPI-Q
Paget’s disease of the bone	Most sensitive diagnostic test is a radionuclide bone scan X-ray can help evaluate focal bone pain Serum ALP is less sensitive, but typically elevated in the setting of normal liver function tests Biochemical markers such as PINP, BALP, NTX, and CTX are elevated in active PDB but do not offer any clear advantage over ALP	Bisphosphonates can help bone pain Surveillance: Check a baseline bone scan, and then recheck if the patient develops symptoms of bone pain in a new site. Serum ALP can be used for follow up every 6–12 months
ALS	Clinical exam shows upper and lower motor neuron signs NCS/EMG shows a disorder of motor neurons	Multidisciplinary clinic with neurologist, PT, OT, SLP, RT, SW, palliative care No consensus on whether to prescribe ALS drugs (riluzole, edaravone) Surveillance: If patients’ weakness becomes more rapid, or they develop UMN signs, bulbar weakness, or respiratory dysfunction, they should be evaluated for ALS clinically and with an EMG. They should be followed every 3 months thereafter
CMT	NCS/EMG shows length-dependent axonal sensorimotor peripheral neuropathy Genetic sequencing confirms diagnosis	PT, OT, ambulatory assistive devices Surgical procedures for foot deformities Surveillance: Check a baseline NCS/EMG, and surveillance via annual physical exams
Parkinson’s disease/ parkinsonism	Clinical exam shows bradykinesia, muscle rigidity, rest tremor, and postural instability DaTScan shows nigrostriatal dopamine deficit	Trial of Sinemet, which if successful can either be continued or switched to another symptomatic dopaminergic agent Surveillance: Check a baseline MDS-UPDRS, and repeat yearly as needed
Cardiomyopathy	Cardiac MRI is the gold standard, although echocardiogram is also useful for assessing cardiac structure and function	ACE inhibitors or ARBs, beta blockers, MRAs AICD or LVAD if severe Surveillance: Check a baseline cardiac MRI and repeat if symptoms arise. If abnormal, repeat every 2 years
Respiratory dysfunction	Serum bicarbonate and PFTs (sitting and supine FVC, MIP, MEP, PCF) show signs of respiratory weakness Sleep study for sleep disordered breathing	Respiratory therapy LVR bag, MI-E, suction device Noninvasive positive pressure ventilation (NIPPV) Up to date vaccinations Surveillance: Check baseline serum bicarbonate, PFTs, and sleep study. PFTs should be repeated annually unless patients have more rapid rate of decline