Forging ahead

Routine serum lactate does not detect D-lactate, which is produced by colonic bacteria and has been reported in short bowel syndrome and following intestinal bypass surgery. This may occur weeks to months after intestinal procedures, following ingestion of a heavy carbohydrate load, and almost invariably presents with altered mental status and increased anion gap metabolic acidosis, although generalized weakness has been reported.

A surgical consultant drained her wound infection. Fluid Gram stain was negative. D-lactate, salicylate and acetaminophen levels were undetectable. Thiamine pyrophosphate level was 229 nmol/L (reference range: 78-185 nmol/L). Acetaminophen was discontinued and N-acetylcysteine infusion was started for possible 5-oxoprolinemia. Her anion gap acidosis rapidly improved. Twelve hours after admission, she reported sudden onset of blurry vision. Her vital signs were: temperature 37^oC, heart rate 110 beats per minute, respiratory rate 40 breaths per minute, blood pressure 168/90, and oxygen saturation 100% on ambient air. Telemetry showed ventricular bigeminy. On examination, she was unable to abduct her right eye; muscle strength was 1/5 in all extremities; biceps, ankle, and patellar reflexes were absent.  

Her neurological deficits have progressed over hours to near complete paralysis, asymmetric cranial nerve paresis, and areflexia. Although botulism can cause blurred vision and absent deep tendon reflexes, patients almost always have symmetrical bulbar findings followed by descending paralysis. Should the “numbness” in her arms reported earlier represent undetected sensory deficits, this, too would be inconsistent with botulism.

A diagnosis of GBS ties together several aspects of her presentation and clinical course. Several variants show different patterns of weakness and may involve cranial nerves. Her tachypnea and dyspnea are concerning signs of potential impending respiratory failure. The ventricular bigeminy and mild hypertension could represent autonomic dysfunction that is seen in many cases of GBS.

She was intubated for airway protection. Computed tomography angiography and magnetic resonance imaging of her brain were normal. Cerebral spinal fluid analysis obtained through lumbar puncture showed the following: white blood cell count 3/μL, red blood cell count 11/μL, protein 63 mg/dL (reference range: 15-60mg/dL), and glucose 128 mg/dL (reference range: 40-80mg/dL).

The lumbar puncture is consistent with GBS given the slightly elevated protein and cell count well below 50/μL. Given the severity of her symptoms, treatment with IV immunoglobulin or plasmapheresis should be initiated. Nerve conduction studies (NCS) and electromyography (EMG) are indicated for diagnostic confirmation.

EMG and NCS revealed a severe sensorimotor polyneuropathy with demyelinating features including a conduction block at a noncompressible site, consistent with AIDP. Left sural nerve biopsy confirmed acute demyelinating and mild axonal neuropathy (Figure 2). On hospital day 2, treatment with IV immunoglobulins (IVIG) was initiated; however, she developed anaphylaxis following her second administration and subsequently received plasmapheresis. A tracheostomy was performed for respiratory muscle weakness, and she was discharged to a nursing facility. C. botulinum cultures from the wound eventually returned negative. Following her hospitalization, a serum 5-oxoproline level sent 10 hours after admission returned as elevated, confirming the additional diagnosis of 5-oxoprolinemia. On follow-up, she can sit up and feed herself without assistance, and her gait continues to improve with physical therapy.

This patient presented with rapidly progressive weakness that developed in the 2 weeks following bariatric surgery. In the postsurgical setting, patient complaints of weakness are commonly encountered and can pose a diagnostic challenge. Asthenia (ie, general loss of strength or energy) is frequently reported in the immediate postoperative period, and may result from the stress of surgery, pain, deconditioning, or infection. This must be distinguished from true neurologic weakness, which results from dysfunction of the brain, spinal cord, nerve, neuromuscular junction, or muscle. The initial history can help elucidate the inciting events such as preceding surgery, infections or ingestions, and can also categorize the pattern of weakness. The neurologic examination can localize the pathology within the neuraxis. EMG and NCS can distinguish neuropathy from radiculopathy, and categorize the process as axonal, demyelinating, or mixed. In this case, the oculomotor weakness, sensory abnormalities and areflexia signaled a severe sensorimotor polyneuropathy, and EMG/NCS confirmed a demyelinating process consistent with GBS.

Guillain-Barré syndrome is an acute, immune-mediated polyneuropathy. Patients with GBS often present with a preceding respiratory or diarrheal illness; however, the stress of a recent surgery can serve as an inciting event. The syndrome, acute postgastric reduction surgery (APGARS) neuropathy, was introduced in the literature in 2002, describing 3 patients who presented with progressive vomiting, weakness, and hyporeflexia following bariatric surgery.¹ The term has been used to describe bariatric surgery patients who developed postoperative quadriparesis, cranial nerve deficits, and respiratory compromise.² Given the clinical heterogeneity in the literature with relation to APGARS, it is probable that the cases described could result from multiple etiologies. While GBS is purely immune-mediated and can be precipitated by the stress of surgery itself, postbariatric surgery patients are susceptible to many nutritional deficiencies that can lead to similar presentations.³ For example, thiamine (vitamin B1) and cobalamin (vitamin B12) deficiencies cause distinct postbariatric surgery neuropathies.⁴ Thiamine deficiency may manifest weeks to months after surgery and can rapidly progress, whereas cobalamin deficiency generally develops over 3 to 5 years. Both of these syndromes demonstrate an axonal pattern of nerve injury on EMG/NCS, in contrast to the demyelinating pattern typically seen in GBS. In addition, bariatric surgery patients are at higher risk for copper deficiency, which usually presents as a myeloneuropathy with subacute gait decline and upper motor neuron signs including spasticity.

Although GBS classically presents with symmetric ascending weakness and sensory abnormalities, it may manifest in myriad ways. Factors influencing the presentation include the types of nerve fibers involved (motor, sensory, cranial or autonomic), the predominant mode of injury (axonal vs demyelinating), and the presence or absence of alteration in consciousness.⁵ The most common form of GBS is AIDP. The classic presentation involves paresthesias in the fingertips and toes followed by lower extremity weakness that ascends over hours to days to involve the arms and potentially the muscles of respiration. A minority of patients with GBS first experience weakness in the upper extremities or facial muscles, and oculomotor involvement is rare.⁵ Pain is common and often severe.⁶ Dysautonomia affects most patients with GBS and may manifest as labile blood pressure or arrhythmias.⁵ Several variant GBS presentation patterns have been described, including acute motor axonal neuropathy, a pure motor form of GBS; ophthalmoplegia, ataxia, and areflexia in Miller Fisher syndrome; and alteration in consciousness, hyperreflexia, ataxia, and ophthalmoparesis in Bickerstaff’s brain stem encephalitis.⁵

Patients with GBS can progress rapidly to respiratory failure. Serial neurologic exams may signal the diagnosis and inform triage to the appropriate level of care. Measurement of bedside pulmonary function, including mean inspiratory force and functional vital capacity, help to determine if there is weakness of diaphragmatic muscles. Patients with signs or symptoms of diaphragmatic weakness require monitoring in an intensive care unit and potentially early intubation. Treatment with IVIG or plasmapheresis has been found to hasten recovery from GBS, including earlier improvement in muscle strength and a reduced need for mechanical ventilation.⁷ Treatment selection is based on available resources as both modalities are felt to be equivalent.The majority of patients with GBS make a full recovery over a period of weeks to months, although many have persistent motor weakness. Despite immunotherapy, up to 20% of patients remain severely disabled and approximately 5% die.⁸ Advanced age, rapid progression of weakness over a period of less than 72 hours, need for mechanical ventilation, and absent compound muscle action potentials on NCS are all associated with prolonged and incomplete recovery.⁹

This patient developed respiratory failure within 12 hours of hospitalization, prior to being diagnosed with GBS. Even in that short time, the treating clinicians encountered a series of clinical diversions. The initial proximal pattern of muscle weakness suggested a possible myopathic process; the wound infection introduced the possibility of botulism; obesity and recent bariatric surgery triggered concern for thiamine deficiency; and the anion gap acidosis from 5-oxoprolinemia created yet another clinical detour. While the path from presentation to diagnosis is seldom a straight line, when faced with rapidly progressive weakness, it is paramount to forge ahead with an efficient diagnostic evaluation and timely therapeutic intervention.