The patient stated she had attempted to stand up from a seated position when she “felt like [she] was going to pass out.” The patient called 911 for assistance. On further discussion, the patient revealed she had experienced one similar episode of weakness earlier in the year, but this had resolved spontaneously and was not as severe. She does not have a primary care physician and she had never sought care for this complaint. The patient said she noticed generalized abdominal pain, nausea, and constipation, associated with each of these episodes of weakness and light headedness. She denied any recent illnesses. She stated she treats her bipolar disorder with daily cannabis and consumes alcohol daily as well.She had no pertinent family history. Her social history included daily alcohol use, drinking a total of 1.75 liters of vodka over a two-week period. She started smoking when she was 16 years old, smoking a pack per day, but quit a year prior to presentation. The patient smoked cannabis daily. Her only medication was ferrous sulfate 325 milligrams daily. She had no known drug or environmental allergies. On physical exam, the patient was alert and in no acute distress but appeared tired. She was able to stand unassisted. At the time of triage, she was afebrile , her heart rate was 40 beats per minute, she was breathing 20 times per minute, her blood pressure was 115/90 millimeters of mercury, and she had an oxygen saturation of 98% on room air. She weighed 77.3 kilograms and was 1.65 meters tall . She was well developed, well nourished and speaking in complete sentences without accessory muscle use. She was oriented as to person, place and time. She was without sensory deficits and had normal muscle tone. Her strength was 4/5 with elbow flexion and extension, hand grip, knee flexion and extension,vertical agriculture and ankle dorsi- and plantar-flexion bilaterally. Deep tendon reflexes were 2+ for the bilateral brachioradialis and patellar reflexes.
No clonus could be provoked. She did not have any cranial nerve defects, and she had a normal gait and station. She had normal range of motion of all four extremities, and she did not have any edema. Her lower extremity compartments were soft in both the thighs and the lower legs bilaterally. She exhibited tenderness around her bilateral shoulders and shins. Her head was normocephalic and without signs of injury. Her oropharynx was clear and moist, and her pupils were equal, round, and reactive to light. Her conjunctiva and extraocular motions were normal. Her neck was supple and had a full range of motion, without jugular venous distention or adenopathy. On cardiovascular exam the patient was bradycardic with a regular rhythm, and she had a normal S1/S2 without gallops, friction rubs, or murmurs. On auscultation her breath sounds were clear without wheezes, rales or rhonchi. Her abdomen was non-distended, soft and non-tender throughout with normal bowel sounds. Her skin was warm and dry, and her capillary refill was less than two seconds. She did not have any rashes. Her mood, affect, and behavior were normal. The patient’s electrocardiogram is shown . The results of the patient’s initial laboratory evaluation are shown in Table 1. A test was ordered, and a diagnosis was made.This case involved a young woman with episodic weakness. She reported near syncope, transient extremity paralysis, and generalized weakness. She reported associated nausea, abdominal pain, and constipation. She also reported regular substance use in the form of marijuana and alcohol. Her review of systems was otherwise unremarkable, and notably it was negative for recent illness or gastrointestinal distress outside of this episode. With this in mind, I began to formulate a differential diagnosis. Episodic weakness, particularly extremity paralysis, suggests metabolic and electrolyte derangements such as hypokalemic periodic paralysis. Weakness may also suggest a primary neurologic condition, including Guillain-Barré syndrome, multiple sclerosis, and other demyelinating disorders. Her GI symptoms could be due to a broad array of abdominal conditions, but her substance use suggests these symptoms may be related to an ingestion. The patient’s bradycardia could be due to disseminated Lyme disease, myocarditis, or other etiologies of heart block. More information is required. I used the information provided by her physical exam to further refine my differential diagnosis. Her physical exam was notable for a tired-appearing female with bradycardia.
Pertinent negative findings included that the compartments of the legs were noted to be soft, clinically excluding a compartment syndrome. Additionally, the patient had no focal neurologic deficits based on the documented neurologic exam. Several findings, including cerebellar signs were not documented, but the patient was noted to have normal gait and station. The mention of normal compartments and the normal neurologic exam suggests that a neurologic cause is unlikely. Further, the case did not provide any imaging studies – notably, there was no neuroimaging included. The patient’s ECG showed a sinus bradycardia with sinus arrhythmia, short QTc with T-wave inversions in aVR and V1, and U waves, but it did not show a heart block. I then reviewed the patient’s laboratory findings. She was noted to have a mild anemia, elevated creatine kinase with myoglobinuria, hematuria, proteinuria, and urinary findings consistent with a urinary tract infection. Additionally, she has multiple electrolyte derangements, including hypokalemia, hyperchloremia with acidosis, hypermagnesemia and hypophosphatemia. She had an elevated creatinine and a mild transaminitis. These laboratory findings suggest her symptoms are due to a metabolic derangement. This patient had a non-anion gap metabolic acidosis. The differential diagnosis for non-anion gap metabolic acidosis includes diarrhea, intestinal fistulae, renal tubular acidosis , ureteroileostomy, ureterosigmoidostomy, toluene use, ketoacidosis, D-lactic acidosis, and administration of chloriderich solutions.After cross-referencing this with the case details, some of these diagnoses can be eliminated based on the history, exam, and review of systems. Specifically, the patient reported constipation, thereby eliminating diarrhea as a cause. She also had no surgical history, hence eliminating ureteroileostomy and ureterosigmoidostomy as causes. Although her diet is not mentioned, there is no reported history of abnormal ingestion of food or fluids; so I reasonably eliminated chloride-rich solution ingestion as a cause. This left proximal and distal RTA, toluene use, ketoacidosis, and under consideration. When cross-referencing these with the case details and laboratory findings once again, some options were not consistent with the presentation. Specifically, there was no ketonuria making ketoacidosis unlikely.
Lactic acidosis is a result of a hypoperfusion state, and the clinical case did not provide any evidence of hypoperfusion making this unlikely as well. There were some additional laboratory findings outside of the metabolic panel that needed to be considered. Namely, the patient’s hemoglobin and hematocrit were slightly abnormal . Also, she had an elevated creatine kinase and myoglobin as well as slight elevation in her aspartate transaminase. Her urine also showed some hematuria, pyuria,hydroponics flood table and proteinuria as well as findings of nitrites and leukocyte esterase. When these labs are considered in conjunction with the metabolic abnormalities, my differential diagnosis now included hypokalemic periodic paralysis, rhabdomyolysis, adrenal insufficiency, proximal and distal RTA, inflammatory myopathy, and poisoning . Adrenal insufficiency can cause metabolic derangements and presents with symptoms including fatigue, weight loss, GI complaints, and myalgias, and may also include psychiatric symptoms. In primary adrenal insufficiency, the potassium is high and sodium is low, which is not consistent with this case. In secondary or tertiary adrenal insufficiency, potassium is normal or low, sodium can be high or low, and chloride is normal with a low glucose.These are not consistent with the findings in this case either; so I eliminated adrenal insufficiency from my differential diagnosis. Inflammatory myopathies present with muscle weakness, cardiac involvement, and laboratory findings including elevated serum creatinine kinase and elevated myoglobin levels in both urine and serum. These patients usually present with acute onset of “antisynthetase syndrome,” constitutional symptoms, Raynaud’s phenomenon, and a nonerosive arthritis.While the laboratory findings here were consistent with a possible myopathy, the clinical presentation was not classic, making this a less likely possibility. Another consideration was rhabdomyolysis potentially resulting from compartment syndrome. Compartment syndrome occurs from increased fascial compartment pressure with subsequent tissue hypoperfusion, which can lead to muscle necrosis and rhabdomyolysis. The classic triad of findings in rhabdomyolysis is muscle pain, weakness, and dark urine. Patients with rhabdomyolysis usually have some combination of highly elevated creatine kinase, myoglobinuria, hyperkalemia, hyperphosphatemia, acute kidney injury, hypocalcemia, and metabolic acidosis with or without an anion gap.4 In this patient’s case, there was no clear inciting event, and her symptoms were episodic with spontaneous resolution. Additionally, she did not complain of focal pain or weakness as would be expected in compartment syndrome. Although she did have an elevated creatine kinase, the elevation was not significant and the expected laboratory findings of hyperkalemia and hyperphosphatemia were not present. I felt that compartment syndrome and rhabdomyolysis were unlikely. In this young adult patient with episodic weakness and hypokalemia, hypokalemic periodic paralysis was immediately considered as part of the differential diagnosis. This condition is characterized by attacks of weakness with a normal neurologic exam in between, as seen in this patient. Primary hypokalemic periodic paralysis follows an autosomal dominant inheritance pattern, and notably this patient had no known family history of the same. Bulbar and respiratory functions are preserved and between attacks, patients will also present with normal plasma potassium. Triggers include stress, exercise, and carbohydrates. The condition also presents with arrhythmias.There are, however, other conditions that can cause non-familial hypokalemic paralysis, including RTA.6 All three sub-types of RTA are characterized by an inability to acidify the urine. As a result of this, RTAs present with an increased urine anion gap, but this information was not provided in the case history. In distal or type 1 RTA, there is impaired hydrogen ion secretion in the distal tubule of the nephron. In proximal or type 2 RTA, there is impaired bicarbonate reabsorption in the proximal tubule of the nephron. In type 4 RTA, there is decreased aldosterone secretion or aldosterone resistance.As a result of this, type 4 RTA is associated with serum hyperkalemia while the other two types of RTA result in hypokalemia.Due to the serum potassium levels, which were not suggestive of aldosterone resistance, I eliminated type 4 RTA from my list of possibilities.In type 2 RTA, urine pH is initially high, then decreases to < 5.5. The urine pH remains above 5.5 in type 1 RTA.This patient had a urine pH of 7.0, suggesting either a type 1 RTA or an early type 2 RTA. Type 1 RTA can be hereditary or be caused by autoimmune diseases such as Sjögren’s syndrome, or as a complication of chemotherapy or toluene use. The causes of type 2 RTA include genetic abnormalities, Fanconi syndrome, monoclonal gammopathy, and carbonic anhydrase inhibitor use.There was no mention of chemotherapy or carbonic anhydrase inhibitors with the patient’s presentation. The patient had no family history of similar issues, and it would stand to reason that a genetic abnormality would have come to light before age 19 years. As such, I feel type 1 RTA is more likely than type 2 RTA. The Agency for Toxic Substances and Disease Registry notes that toluene is a solvent found in paints, nail polish, paint thinners, and adhesives, among other substances. It can have toxic effects if ingested or inhaled.The findings of acute toluene use include a hypokalemic paralysis and a metabolic acidosis. Patients are also often found to have liver injury andrhabdomyolysis, and may present with altered mentation, renal failure, and acidemia.This patient’s presentation is most consistent with type 1 RTA due to toluene use. She denied any illicit drug use but did admit to a history of alcohol ingestion and marijuana use, raising the question of whether there could be toxic alcohols or other coingestions. Unfortunately, there is no diagnostic test for toluene use. However, proximal and distal RTA can be differentiated by calculating the urinary ammonium ion concentration from the measured urine anion gap and osmolar gap. Therefore, my test of choice would be a urine electrolyte panel to calculate the anion gap and osmolar gap. Additionally, I would consult nephrology to assist in management of this patient.