Can’t Shake This Feeling

The approach to clinical conundrums by an expert clinician is revealed through the presentation of an actual patient’s case in an approach typical of a morning report. Similarly to patient care, sequential pieces of information are provided to the clinician, who is unfamiliar with the case. The focus is on the thought processes of both the clinical team caring for the patient and the discussant.

A 78-year-old woman presented to her primary care physician with a 2-month history of progressive leg weakness. She reported walking difficulty caused by occasional “buckling” of the knees.

The knee buckling may be a clue to the quadriceps muscle weakness. The quadriceps straightens and locks the knee when the foot is being planted. Weakness of this muscle can result in the knee giving way. Isolated quadriceps weakness, which is uncommon, typically is caused by lower motor neuron issues, such as femoral neuropathy, L4–L5 radiculopathy, lumbosacral plexopathy, and primary muscle diseases, including inclusion body myositis.

The patient had diabetes mellitus and hypertension. Her medications were insulin glargine, metformin, glipizide, lisinopril, atorvastatin, and aspirin, and she was taking vitamin D and calcium. None of these was recently changed or added. Aside from having the weakness, the patient was in her usual state of health and had no other complaints. She denied weight changes, fevers, night sweats, and fatigue. She was widowed, lived with her daughter, had no pets, never used tobacco, and did not drink alcohol or use illicit drugs. There was no family history of neuromuscular disorders, and both of her parents died of natural causes at advanced ages.

The physical examination revealed no knee deformities, and the patient had good active range of motion of both knees and normal strength throughout her limbs. Plain radiographs of the knees showed mild medial compartment osteoarthritis. The patient was advised to stop atorvastatin.

Patients who take atorvastatin and other statins (3-hydroxy-3-methyl-glutaryl-co-enzyme A reductase inhibitors) can experience a spectrum of muscle disease, from myalgias and weakness to (rare) overt myositis with rhabdomyolysis. Statin-induced myopathy tends to affect larger proximal muscles, can occur at any time during the period the medication is being used, and usually resolves within weeks after discontinuation. Given this patient’s preserved strength, it was reasonable to manage her conservatively.

One month later, she presented to another hospital’s emergency department with increasing weakness in the lower extremities and new loss of balance requiring use of a walker for ambulation. She thought the weakness was confined to her legs and was affecting her thigh muscles more than her calves or feet. She reported fatigue, decreased appetite, and an unintentional 15-pound weight loss. She denied diarrhea, back pain, bowel and bladder function problems, sensation changes, myalgias, and arthralgias. She reported no swallowing or vision problems, rashes, Raynaud disease symptoms, photosensitivity, dry eyes or mouth, recent falls or trauma, fevers, night sweats, recent illness, or travel.

On physical examination, the patient’s temperature was 98.2°F, blood pressure 120/84 mm Hg, pulse 73 beats per minute, respiratory rate 16 breaths per minute, and oxygen saturation 99% with ambient air. The patient was obese and not in distress. She was alert, oriented, and able to follow multistep instructions. Cranial nerve examination was normal. The patient had mild weakness in her bilateral deltoids and bilateral hip flexors but full strength in all other muscle groups. Deep tendon reflexes were normal in the biceps and patella and reduced in the ankles. The Babinski sign was absent. Throughout the lower extremities, sensation was intact to light touch; there was no saddle anesthesia. Finger–nose–finger testing showed slight dysmetria in the left upper extremity. Because of her imbalance, the patient needed help to stand up; once upright, though, she was able to take 3 steps forward and backward with use of a walker. Her stride length was diminished, and her gait unsteady and wide based.

These exam findings suggest 2 separate localizations. Symmetric proximal weakness with preserved distal strength in the extremities indicate a lower motor neuron problem, further suggested by the absence of upper motor neuron findings of spasticity, and hyperreflexia. Intact patellar and biceps reflexes suggest either muscle or neuromuscular junction localization. Separately, the findings of wide-based gait and dysmetria raise the possibility of a problem in the ipsilateral cerebellum, in this case on the left. A cerebellar lesion would not explain the bilateral symmetric weakness. The combination of lower motor neuron leg weakness and cerebellar deficits suggests a systemic disorder, such as an infectious, inflammatory, or paraneoplastic process. A space-occupying lesion would not produce this constellation of deficits.

Serum chemistry panel was normal, creatinine level 0.47 mg/dL, and albumin level 4.0 g/dL. White blood cell (WBC) count was 8100/mm³, hemoglobin level 12 g/dL, and platelet count 287,000/mm³. Alanine aminotransferase (ALT) level was 74 U/L (reference range, 0-36 U/L), alkaline phosphatase level 41 U/L (reference range, 37-117 U/L), and total bilirubin level 0.4 mg/dL (reference range, 0.2-1.2 mg/dL). Prothrombin time and thyrotropin were normal. Creatine kinase (CK) level was 2328 U/L (reference range, <200 U/L). Erythrocyte sedimentation rate was 17 mm/h, and C-reactive protein level 0.1 mg/L. Urinalysis (dipstick testing) detected no myoglobin, and there were no casts. Plain radiograph of the chest was normal.

The elevated CK indicates muscle disease, and, in the absence of other findings of liver disease, the ALT elevation likely has a muscle origin as well. The differential diagnosis for elevated CK includes myopathy caused either by infection, trauma, ischemia, or a toxin (medication included) or by a hereditary, metabolic, endocrinologic, or inflammatory disorder. There is no history of trauma, strenuous exertion, or muscle toxin other than the statin, and the progression of symptoms after medication discontinuation argues against statin myopathy. The laboratory test results rule out derangement of potassium, calcium, phosphorus, magnesium, vitamin D, or thyroid function as the cause of the myopathy. The absence of fever, absence of diffuse organ involvement, and normal inflammatory markers point away from a systemic infection or vasculitis. The inflammatory myopathies dermatomyositis and polymyositis classically produce proximal muscle weakness and are possibilities in this case, but one would expect the inflammatory markers to be elevated in these conditions. Malignancy related to dermatomyositis or to paraneoplastic syndrome may account for the myopathy.