Weakness - Differential Diagnosis Framework



Approach To Weakness:

 • Non-neuromuscular disorder (Cardiac, pulmonary etc)

 • CNS -> PNS -> NMJ -> Muscle

 • Muscle weakness (generalized, distal, proximal, or localized)



1. Upper Motor Neuron Impairment:

 • Acute stroke syndromes

 • Space occupying lesions of the central nervous system: Brain tumor

 • Lesions of the spinal cord

 • Inflammatory: Vasculitis

 • Infectious: Brain abscess

 • Toxic/drug: Radiation

 • Metabolic/endocrine: Vitamin B12 deficiency

 • Congenital leukodystrophies



2. Lesions Of The Peripheral Nervous System:

 • Symmetric polyneuropathy: DM

 • Mononeuropathy: Nerve compression

 • Mononeuritis multiplex (DM, Vasculitis-polyarteritis nodosa)

 • Toxic/drug: Lead

 • Neoplastic: Paraneoplastic syndrome

 • Inflammatory: Myeloma/amyloid

 • Infectious: Leprosy



3. Neuromuscular Junction:

 • Exercise-induced weakness: Fatiguability - Consider NMJ

 • Nerve Side Presynaptic:

	- Lambert-Eaton

	- Isaacs' syndrome

	- Tick-paralysis

	- Botulism

	- Aminoglycosides

	- Envenomation (venom from animal bites)

 • Synaptic Cleft:

	- Organophosphate toxicity

	- Carbamate toxicity

 • Muscle Side:

	- Postsynaptic: Myasthenia Gravis

	- Lack of UMN/LMN signs

	- Lack of sensory changes

	- Common pattern: Symmetric proximal weakness



Myopathy:

 • Inflammatory disorders: Polymyositis

 • Immune mediated necrotizing myopathy

 • Autoimmune: Inclusion body myositis

 • Endocrinopathies: Hypothyroid

 • Metabolic myopathies: Hypoglycemia

 • Drugs and toxins: Steroids, Statins, amiodarone, Alcohol

 • Infections:

	- Viral - Influenza, parainfluenza, Coxsackie, HIV, CMV, EBV

	- Bacterial - Pyomyositis, Lyme myositis

 • Rhabdomyolysis

 • Neoplastic: Malignancy-associated myositis

 • Genetic: Muscular dystrophies



Work Up:

 • Chem: CPK aldolase, lactate dehydrogenase, and the aminotransferases

 • Serology:

	- Anti-Ro/SSA, anti-La/SSB, anti-Sm, and anti-RNP

	- (Myositis) anti-histidyl-t-RNA synthetase [anti-Jo-1]

	- (Vasculitis) ANCA titers, hepatitis B and C serologies, and cryoglobulins

 • PNS, NMJ, Nerve: Nerve conduction and electromyographic (EMG) studies

 • MRI: Inflammation of the muscle

 • Muscle Biopsy: Dermatomyositis, polymyositis, inclusion body myositis, certain drug-induced myopathies, the muscular dystrophies, or vasculitis



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