An 87-year-old Caucasian man was transferred from another hospital after an episode of altered mental status secondary to hypercapnea requiring intubation. His past medical history included type 2 diabetes, stage 3 chronic kidney disease, and heart failure with preserved ejection fraction. He was a lifelong non-cigarette smoker. Per the family he was complaining of shortness of breath, weight gain and worsening leg swelling for 3 weeks, and was progressively more somnolent over the last week. On admission to the outside hospital the results of his laboratory tests were significant for a normal blood glucose of 176mg/dL, normal white blood cell count at 7000 cells/mm3, creatinine of 1.6mg/dL (at his baseline), elevated brain natriuretic peptide at 778pg/mL and negative toxicology screen. He had no history of opioid or benzodiazepine usage. His ABG showed acute on chronic hypercapnea with a pH of 7.22, partial pressure of carbon dioxide (pCO2) of 83mmHg and bicarbonate (HCO3) of 36mmol/L requiring intubation explaining his altered mental status. He was noted to be in congestive cardiac failure and was given diuretics and eventually he was extubated. He was transferred to our institution on nightly bilevel positive airway pressure (bipap) for his unexplained hypercapnic failure. His only complaint on transfer was his chronic two-pillow orthopnea.\nOn arrival he was in no acute distress with a heart rate of 74, respiratory rate of 20, blood pressure of 107/65mmHg, and oxygen saturation of 98% on 2L nasal cannula. A cardiovascular and respiratory system examination was unrevealing with normal jugular venous pressure and normal cardiac examination. There was paradoxical abdominal motion with the abdominal wall moving inwards on inspiration. A neurologic examination revealed 3/5 strength in his left deltoid and decreased biceps reflexes bilaterally. Power, tone and reflexes were normal in both his lower limbs. He also had severe osteoarthrosis of distal and proximal interphalangeal joints bilaterally with Heberden’s nodes.\nHis ABG on room air showed a partial pressure of oxygen of 64mmHg, pCO2 of 53mmHg, HCO3 of 28mmol/L and a pH of 7.33 with a normal A-a gradient of 18. This was consistent with chronic respiratory acidosis secondary to hypoventilation, given the normal A-a gradient. A chest X-ray showed elevated hemidiaphragms bilaterally (Figure ). Pulmonary function testing showed a restrictive pattern with a normal ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of 0.79 (114% predicted), with FEV1 and FVC 49 and 42% of predicted respectively. There were also significantly decreased maximum inspiratory and maximum expiratory pressures of 27.2 and 31.4% predicted; and a decrease in FVC of 22% from the sitting to supine position suggestive of neuromuscular weakness (>20%). The diffusing capacity was normal suggesting a chest wall or neuromuscular cause of restrictive lung mechanics.\nGiven his abnormal neurologic examination with left deltoid weakness and decreased biceps reflexes, our differential included respiratory neuromuscular weakness from cervical spondylosis and phrenic nerve root compression (given the C5 neurological deficits); or possible cervical myelopathy at C5/C6. The absent biceps reflex (C5 and C6) raised suspicion for myelopathy at the C5 to C6 level although this is typically associated with a brisk triceps reflex (C7). The lack of neurological findings in his lower extremities also argued against myelopathy, but given the potential variable manifestations of cervical myelopathy, an electromyogram (EMG) and nerve conduction study (NCS) were performed. The EMG and NCS revealed decreased amplitude in the phrenic nerves bilaterally and radiculopathy in his upper limbs, suggestive of nerve root compression at the cervical foraminal level. There was no evidence of amyotrophic lateral sclerosis or myopathy on EMG/NCS and serum creatine phosphokinase was normal. A cervical MRI was performed and showed severe bilateral foraminal narrowing at C3, C4 and C5 with no evidence of myelopathy, confirming the diagnosis of phrenic nerve root compression from cervical spondylosis as the cause of hypoventilation. When he developed pulmonary edema, the resultant decreased lung compliance placed an increased respiratory load on his weakened neuromuscular apparatus leading to worsening hypercapnea and resultant metabolic encephalopathy with altered mental status. Carbon dioxide, being readily diffusible across the blood–brain barrier is a well-known cause of encephalopathy in the setting of hypercapnea.\nHe was offered surgical decompression of cervical motor roots or possible diaphragmatic pacing. Given his age, he opted for conservative management with nightly bipap to rest his respiratory muscles at night. He showed significant improvement with night-time bipap and felt less fatigued during the day, probably from the rest provided to his respiratory neuromuscular apparatus. Following discharge he remained stable but gradually became less compliant with bipap. He had four admissions in 2 years with hypercapnic respiratory failure in the setting of pulmonary edema from heart failure. Pulmonary edema and the resultant decreased lung compliance placed an increased respiratory load on his weakened neuromuscular apparatus. As expected he fatigued more easily with his weakened neuromusculature leading to hypoventilation and worsening hypercapnea. He required continuous bipap while hospitalized until diuresis improved chest wall compliance and respiratory mechanics. He continued to refuse invasive therapies and was managed conservatively with nightly bipap. He developed evidence of right ventricular failure and pulmonary hypertension on echo from a combination of pulmonary venous hypertension from heart failure and chronic hypoxia from hypoventilation secondary to his neuromuscular weakness. Given his recurrent episodes of respiratory failure and worsening heart failure he was eventually transitioned to hospice care.
Our in-patient rheumatology service evaluated a 17-year-old Hispanic woman for pain in the neck, low back, bilateral hip, and knee as well as for headaches and morning stiffness lasting two months. At her initial hospitalization two weeks into the disease course, and at six weeks prior to rheumatology evaluation, the hospital service noted that she had decreased range of motion in her neck secondary to pain. Plain radiographic films of the cervical spine (Figure ) revealed no abnormalities, and she was discharged with a course of naproxen. Non-steroidal anti-inflammatory drugs (NSAIDs) offered only minimal relief of symptoms, which prompted an out-patient orthopedics community evaluation and resulted in diagnosis of 'gluteal strain' and bursitis. She was placed on propoxyphene/acetaminophen and cyclobenzaprine, but they did not improve her symptoms.\nDue to the unremitting nature of our patient's symptoms two months into her illness, her pediatrician obtained laboratory studies and a bone scan which revealed abnormal uptake in the right seventh rib (possibly due to prior fracture), increased uptake in the left distal femur and anterior superior left tibial spine, and focal uptake at the facets of several thoracic vertebrae. Her erythrocyte sedimentation rate (ESR) was 49 mm/hour and high-sensitivity C reactive protein was 44.7 mg/L. Concerned about infection or malignancy, our patient's physician readmitted her to our institution. She did not have, then or previously, a history of fever, lymphadenopathy, bleeding or easy bruisability, weight loss, gastrointestinal symptoms, cardiac murmur, or rashes. Stool guaiac results were negative, and an abdominal ultrasound showed no abnormalities. A complete blood count was without cytopenias except for mild normocytic anemia.\nA rheumatological evaluation revealed an obese (body mass index (BMI) 42, greater than 97%) adolescent with findings of point tenderness in her bilateral inferior patella, lower sacrum, and anterior hips. She had a reduced range of motion with muscle spasms in her neck, but no psoriatic lesions or nail pitting. Her spinal symptoms were most severe in the morning and improved with movement and NSAID use. Her family history was positive for idiopathic iritis (father) and inflammatory bowel disease with spondyloarthritis (paternal aunt). A rheumatoid factor was non-reactive, and anti-nuclear antibody was not detected. Creatine kinase and aldolase levels were within normal limits. A HLA-B27 marker was present in our patient. Imaging studies were consistent with an inflammatory process: a hip ultrasound revealed bilateral hip effusions, and a lower extremity MRI revealed T2 abnormal signals in patellar tendon insertions and subcutaneous tissue anterior to the inferior aspect of the left patellar tendon. Prior to her rheumatology evaluation, our patient was given celecoxib (as prescribed by her family physician), which provided significant pain relief in her back and reduction of morning stiffness. Our pediatric rheumatologist diagnosed our patient with undifferentiated spondyloarthritis using the European Spondyloarthropathy Study Group (ESSG) classification criteria (inflammatory spinal pain, hip synovitis, positive family history of HLA-B27-associated diseases, and enthesopathy/enthesitis). The family and our pediatric rheumatologists opted to keep our patient on celecoxib and have close out-patient follow-up because her musculoskeletal pain decreased and her inflammatory markers improved, Although her hip, back, and knee pain improved, our patient continued to have persistent neck pain with symptoms of occipital neuralgia after three months of scheduled NSAID therapy. New plain radiographic imaging of the cervical spine revealed a reversal of the normal lordotic curvature, and a 10 mm distance between the odontoid and anterior arches of C1 had markedly increased since prior films (Figure ). A computed tomography (CT) scan of the cervical spine showed evidence of bony erosion at the tip of the odontoid as well as mild rightward rotatory subluxation of C1, with moderate cervical stenosis at C1 and minimal flattening of the spinal cord (Figure ). This was confirmed on MRI (Figure ), which also demonstrated inflammation around the apical and transverse ligaments and adjacent pannus formation. There was no signal abnormality within the cord itself.\nAt this point, doctors were concerned about our patient's joint instability and referred her to the neurosurgery department. She had no recent history of travel, fever, pharyngitis, torticolis, or trauma. Results of a general examination showed our patient was obese but otherwise normal. She was awake and alert, with full strength throughout. Her left upper extremity was hyper-reflexive compared to her right upper extremity, and her right lower extremity was hyper-reflexive compared to her left lower extremity. Proprioception was intact. She had up-going toes bilaterally but no clonus or Hoffman sign. She had a steady gait with no sway on Romberg testing. Because clinical and radiographic evaluations showed evidence of atlantoaxial instability in the setting of undifferentiated spondyloarthritis, our neurosurgeons recommended a C1-2 fusion to our patient and her family. The doctors postulated that inflammation-mediated ligamentous laxity was causing joint instability but that ongoing infection did not cause the cervical spine disease (Grisel's syndrome). Her anti-inflammatory medication was stopped about one week prior to surgery.\nAfter our patient was fiber-optically intubated with in-line stabilization, we placed needle electrodes for intra-operative neurophysiological monitoring. Then, we measured and recorded baseline somatosensory-evoked potentials, motor-evoked potentials, and free-run electromyography (EMG) readings from the upper and lower extremities. Our patient was then positioned prone using the Mayfield three-point fixation system and a Jackson table; there was no change in her electrophysiology monitoring after positioning. Using fluoroscopy, we checked alignment of the cervical spine, finding a decrease in the atlantodental interval from pre-operative studies. Then, we made a midline incision over the spinous processes and dissected, in standard sub-periosteal fashion, the paraspinous muscle from the spinous processes and laminae. Subsequently, we isolated and bilaterally divided the C2 nerve roots and clearly identified bilaterally the C1 lateral masses, C2 pars, and C1-2 facet complexes. Under fluoroscopic guidance, we placed C1 lateral mass screws: a 4.0 × 34 mm screw on the right and 4.0 × 32 mm screw on the left (Vertex; Medtronic Sofamor Danek, Memphis, TN USA). Then, we placed bilateral, crossing, 3.5 × 24 mm translaminar C2 screws. We performed a C1 laminectomy to ensure that the cervical cord was well decompressed; decorticated the bone; and placed the C1 laminectomy autograft over the denuded surfaces using bone morphogenetic protein (Infuse; Medtronic Sofamor Danek, Memphis, TN USA) and bone matrix (Mastergraft; Medtronic Sofamor Danek) to supplement the graft. We then placed the rods, performed the final tightening, and closed the wound in a layered fashion. Intra-operative-evoked potentials revealed no changes during the case. There was no spontaneous EMG activity. In the immediate post-operative period after waking from general anesthesia, our patient was at her baseline examination levels.\nAt two weeks after surgery, our patient was restarted on celecoxib. Poor wound healing and drainage required antibiotic coverage and delayed initiation of immunomodulation. At four weeks after surgery, our patient received a methylprednisolone infusion (1 g) and was started on adalimumab (40 mg subcutaneously every other week (actual text of hospital formulary)) eight weeks after her operation. She has had relief from neck pain and remains neurologically intact except for soft signs of myelopathy, which were found pre-operatively. There was no evidence of abnormal motion between the C1 and C2 vertebrae or evidence of instrumentation failure on dynamic cervical spine X-rays (Figure ). While maintained on adalimumab, our patient has had intermittent complaints of hip and knee pain exacerbated by weather changes. Inflammatory markers have remained within normal limits since our patient started adalimumab (even during mild clinical flares). She has not developed psoriasis and there has been no evidence of sacroiliitis or irritable bowel disease (IBD) on MRI scans during a two-year follow up period.