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 #Weakness #Differential #Diagnosis #neurology
