A Collection of Pain-Associated Disorders

Cerebral Venous Thrombosis

Naureen Rafiq, MBBS, Rahila Chaudhry, MD, and Helenka Stone, MD
Creighton University School of Medicine, Omaha, Nebraska

A 26-year-old woman, 8 months postpartum, presented to the emergency department with nausea, a throbbing headache, and blurry vision, but without photophobia, diplopia, neck pain, focal weakness, numbness, or seizure-like activity. She denied having experienced similar symptoms before pregnancy or in the immediate postpartum period.

History. The patient had no significant past medical, social, or family history. Her only medication was an etonogestrel contraceptive implant.

Physical examination. On physical examination, the woman was hemodynamically stable. She had bilateral papilledema with no focal neurologic deficits.

A lumbar puncture with normal opening pressure did not relieve the symptoms of headache and blurry vision.

Diagnostic testing. Laboratory studies revealed a moderately elevated homocysteine level, but the study results were otherwise normal. A computed tomography (CT) scan of the brain without contrast (Figure 1) showed no evidence of infarct, mass effect, midline shift, or hemorrhage; however, a concerning finding of abnormally increased attenuation in the superior sagittal sinus on the CT scan led to further evaluation with magnetic resonance venography (MRV) (Figure 2). MRV demonstrated a complete absence of flow in both the superior sagittal sinus and the left transverse sinus, confirming the diagnosis of cerebral venous thrombosis (CVT).

Discussion. CVT is a vascular disease that can affect any population. It has a prevalence of approximately 5 cases in 1 million people, accounts for 0.5% of all strokes, and has a mortality rate of less than 10%.¹

As with other thrombotic disorders, patients with hypercoagulable conditions are at greater risk of developing CVT. These hypercoagulable conditions include genetic and acquired prothrombotic disorders, cancer, systemic inflammatory disorders, pregnancy, and infections. Local factors such as arteriovenous malformations and head trauma also can increase the risk of developing CVT. In any given patient, the cause of the disease usually is multifactorial.¹

Patients with CVT commonly present with headache, seizures, focal neurologic deficits, altered mental status, and papilledema (each symptom in isolation or concurrently with other symptoms). Symptoms can vary based on the location of the thrombosis. Papilledema is more common in delayed presentations or in chronic thrombosis. Rarer symptoms include subarachnoid hemorrhage, migraine with aura, transient ischemic attacks, tinnitus, and isolated psychiatric symptoms.¹

The diagnosis can be made using MRV and CT, which show filling defects within the affected dural venous sinuses,² as the case presented here demonstrates.

A negative D-dimer assay should not be used to rule out CVT in the setting of an isolated headache.³ Anticoagulation is the mainstay of treatment, although in some cases a patient may require endovascular thrombolysis, therapeutic lumbar puncture, or surgical decompression if intracranial hypertension is present.¹

Although the identification of CVT has improved significantly with modern imaging technology, the diagnosis still is frequently missed because of the wide variation in presenting symptoms. Therefore, it is important for primary care providers to keep a high suspicion for CVT in the appropriate clinical setting, since early diagnosis and intervention significantly improve outcomes.

Differential diagnosis. A number of conditions must be ruled out in the differential diagnosis of CVT (Table).

Idiopathic intracranial hypertension (IIH) is defined by increased intracranial pressure without a mass lesion or other underlying cause. It occurs primarily in obese young women and is diagnosed by way of a lumbar puncture.⁴ Although brain imaging results typically are normal, transverse sinus stenosis has been correlated with IIH.²

Brain arteriovenous malformations (AVMs) are congenital vascular defects characterized by shunting of blood from arteries to veins, usually in a mass of vessels that forms a nidus. Approximately half of persons with the condition present with severe headache after acute rupture of an AVM, while the remainder present with seizure or a focal neurologic deficit. The peak age of presentation is 20 to 40 years, with an estimated prevalence of 0.2% in the general population. The AVM nidus is a high-flow lesion and can be visualized with noncontrast CT, CT angiography, or magnetic resonance imaging (MRI).⁵

Subdural empyema is a collection of purulent material between the dura and the arachnoid matter, most often within the cranium. This life-threatening condition usually is precipitated by sinus, ear, meningeal, or pulmonary infection; sinus or cranial surgery; or cranial trauma. The diagnosis is made with gadolinium-enhanced MRI or contrast CT, which show a peripherally enhancing extra-axial cerebrospinal fluid collection.⁶

References:

1. Bousser M-G, Ferro JM. Cerebral venous thrombosis: an update. Lancet Neurol. 2007;6(2):162-170.
2. Leach JL, Fortuna RB, Jones BV, Gaskill-Shipley MF. Imaging of cerebral venous thrombosis: current techniques, spectrum of findings, and diagnostic pitfalls. Radiographics. 2006;26(suppl 1):S19-S41.
3. Crassard I, Soria C, Tzourio C, et al. A negative D-dimer assay does not rule out cerebral venous thrombosis: a series of seventy-three patients. Stroke. 2005;36(8):1716-1719.
4. Wakerley BR, Tan MH, Ting EY. Idiopathic intracranial hypertension. Cephalalgia. 2014;35(3): 248-261.
5. March BT, Jayaraman MV. Aneurysms, arteriovenous malformations, and dural arteriovenous fistulas: diagnosis and treatment. Semin Roentgenol. 2014;49(1):10-21.
6. Gladstone J, Bigal ME. Headaches attributable to infectious diseases. Curr Pain Headache Rep. 2010;14(4):299-308.

Acknowledgement: The authors thank Shawn Stone, MD, for professional assistance with obtaining and describing the images presented here.

Trigger Finger

Edward J. Shahady, MD
University of Miami, Florida

Willis Paull, PhD
Florida Atlantic University, Boca Raton

A 48-year-old woman presented with finger and knuckle pain in her right hand of 1 year’s duration. She was right-handed. The pain was located over the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the woman’s index and middle fingers. The pain recently had become more intense, which made it difficult for her to sleep and to grasp objects.

History. When she awoke in the mornings, the index and middle fingers of her right hand were stiff and seemed to be stuck in flexion at the PIP joint; she had to force them into extension. Once the fingers were extended, however, there was no extension deficit. The stiffness, as well as the pain, hindered her ability to pick up a cup or to twist a cap off a bottle.

For the past 5 years, the patient had had type 2 diabetes that was not well controlled. She had noticed some “arthritis” in her left shoulder and right knee in the past, and adhesive capsulitis of the left shoulder had been diagnosed 3 years earlier.

Physical examination. The knuckles of her right index and middle fingers were somewhat swollen. She denied numbness, tingling, and loss of sensation.

Differential diagnosis. Rheumatoid arthritis (RA) is a possibility, but RA usually is bilateral and symmetric. If joints other than those in the hands are involved, they are typically small rather than large ones. This patient had no involvement of the left hand, and the other symptomatic joints—the shoulder and knee—were large.

Dupuytren contracture should be considered, because it is more common in patients with diabetes than in those without it. This condition is caused by contracture of the palmar fascial bands, which results in flexion contracture of the MCP and PIP joints, contraction of the flexor tendon apparatus, and contraction of the skin itself. The contracture develops over time and is not reversible. Physical examination is needed to definitively rule out Dupuytren contracture; however, the lack of a permanent contracture (ie, her ability to “unstick” the contracture) favors another diagnosis.

Carpal tunnel syndrome usually affects only the thumb and index finger, and it commonly presents with some sensory symptoms. Moreover, contraction deficits are not typical in carpal tunnel syndrome. Nonetheless, it is important to test for signs of median nerve compression.

Because this patient already had signs of disease in other large joints, osteoarthritis (OA) is a definite possibility. She could have erosive OA, an uncommon type of primary OA that occurs mainly in middle-aged women. Erosive OA primarily affects the interphalangeal joints of the hands but can be present in other hand and wrist joints. Radiographs help rule out this entity: in erosive OA, plain films reveal joint erosions, joint space loss, and peripheral osteophytes. However, the involvement of joints that are seldom affected in erosive OA and the presence of locking in flexion make this diagnosis less likely.

Flexor tenosynovitis, or trigger finger, is the most likely diagnosis. Trigger finger is characterized by painful locking or snapping of the finger as it is flexed and extended. The condition is caused by inflammation and swelling of the flexor tendon sheath, which inhibits the normal back-and-forth gliding motion of the tendon; it affects primarily the superficial and deep flexor tendons at the metacarpal head. Figure 1 shows the area of involvement. Trigger finger usually affects the dominant hand of middle-aged women and is more common in patients with diabetes or RA.

Figure 1. In flexor tenosynovitis, also known as trigger finger, a nodule on the flexor tendon (red arrow) becomes trapped behind the thickened tendon sheath (black arrow), usually at the metacarpophalangeal joint, and the finger becomes stuck in the flexed position.

This patient’s presentation was classic: Her fingers became locked in extension, and she was a middle-aged woman with diabetes.

Trigger finger is a clinical diagnosis, and no other studies are indicated to make the diagnosis. Studies to rule out other causes, such as a measurement of rheumatoid factor would be overkill at this time and would unnecessarily increase the cost of care. The more reasonable approach is to focus energy and resources on treatment of the patient’s trigger finger and control of her diabetes. If the treatment is not successful or if other signs or symptoms become evident, then additional studies would be warranted.

Discussion. Although a patient with trigger finger may have complained of PIP joint pain, palpation of the joint usually reveals minimal to no pain. Passive extension of the DIP or PIP joint while the MCP joint is flexed is usually painless and does not provoke triggering.

The most significant clue to trigger finger is localization of the disorder at the level of the MCP joint. There is almost always palpable tenderness over the volar aspect of the metacarpal head; sometimes a palpable tender nodule is present. Swelling of the finger also may be noted. Active opening and closing of the hand produces painful triggering as the inflamed tendon passes through the constricted area of the sheath. Results of a neurologic examination (including tests for strength, sensation, and reflexes) usually are normal, except in severe cases that are associated with disuse, weakness, or atrophy.

In this patient, physical examination revealed minimal swelling, triggering, and significant tenderness and palpable nodules over the MCP joints of the index and middle fingers.

Treatment. The initial treatment focuses on reducing the inflammation that surrounds the tendon. Activities that involve repetitive grasping and gripping or heavy lifting should be curtailed or avoided. A splint that prevents flexing and locking during sleep can be worn at night. Nonsteroidal anti-inflammatory drugs (NSAIDs) might be prescribed; if they are, a nonselective cyclooxygenase 1 (COX-1) inhibitor, such as ibuprofen (600 mg, 3 times a day for 10 days), would be most appropriate for this patient. Because she has diabetes, COX-2 inhibitors should be used with caution.

Corticosteroid injection at the area of thickening in the tendon sheath or in the nodule is considered first-line therapy by many clinicians. The needle is inserted over the hand’s palmar aspect, distal to the metacarpal head, as shown in Figure 2. The injections can be repeated at 3- to 4-week intervals; they produce relief in 60% to 70% of patients. A maximum of 3 injections is suggested before seeking alternative treatments.¹

Figure 2. Corticosteroid injection at the area of thickening in the tendon sheath relieves trigger finger symptoms in most patients. Use a 1-inch 25-gauge needle directed proximally at a 30° angle toward the nodule or thickened tendon sheath at the MCP joint.

Outcome of the case. The patient was treated conservatively with corticosteroid injections and NSAIDs and did well. Trigger finger may be more refractory to nonoperative management in patients in whom both hands are affected and in those who have diabetes or RA. Surgery is reserved for patients in whom conservative therapy fails. However, surgical release relieves symptoms in most patients. 

Reference:

1. Faunø P, Andersen HJ, Simonsen O. A long-term follow-up of the effect of repeated corticosteroid injections for stenosing tenovaginitis. J Hand Surg (Br). 1989;14(2):242-243.

Rheumatoid Arthritis and Concomitant Tuberculosis

Navin M. Amin, MD
University of California at Irvine

A 40-year-old woman was admitted to the hospital after presenting with a 3-week history of high fever, chest pain, and a dry, irritating cough.

History. The patient had a history of rheumatoid arthritis (RA) and had been under the care of a rheumatologist. Initially, she had been treated with ibuprofen, then with corticosteroids and hydroxychloroquine. During the past 12 months, she had received a weekly injection of infliximab. No tuberculin skin test had been done before the initiation of infliximab therapy, because the patient told the rheumatologist that the results of a tuberculin skin test the year before had been negative.

Her illness had begun insidiously with increasing right upper chest pain that was sharp, pleuritic, and rated a 6 on a pain scale of 1 to 10. The pain was associated with temperatures of up to 38.8°C and chills, rigors, and profuse sweating that increased in the evening. Worsening dyspnea was accompanied by a drop in effort tolerance.

The patient had been seen at a local urgent care center and treated with levofloxacin for a week. A chest radiograph showed infiltrates in the right upper lobe. The symptoms worsened, and the medication was switched to clarithromycin, but there was no marked improvement.

The patient’s appetite was poor, and she had lost 2.75 kg in the past 3 weeks. She denied hemoptysis, palpitations, ankle edema, lymphadenopathy, rash, and joint swelling. The woman had no history of nausea, vomiting, diarrhea, abdominal pain, jaundice, hematemesis, melena, headache, vision problems, seizures, syncope, weakness, paresthesias, urinary symptoms, or bleeding diathesis.

Both of her parents had type 2 diabetes; a younger brother had bronchial asthma. The patient smoked half a pack of cigarettes a day; she did not drink alcohol or use illicit drugs. She was sexually monogamous. She had visited her grandparents in Mexico for 2 weeks a year ago.

Physical examination. The thin woman appeared chronically ill. Her hands showed changes consistent with chronic RA, including swan neck deformity.

Heart rate was 122 beats/min and regular, temperature was 38.8°C, respiratory rate was 24 breaths/min, and blood pressure was 118/68 mm Hg. Her weight was 47 kg. Hydration status was good. Examination of the head and neck showed no icterus, erythema, or evidence of candidal infection. The mucosa and skin were pale; there were no rashes or tattoos. There was no palpable lymphadenopathy or ankle edema; the thyroid was not palpable. Chest movements were symmetric and equal bilaterally. The trachea was centrally located, and the chest was resonant to percussion. Breath sounds were harsh in the right upper zone, and coarse rales were heard. The jugular venous pressure and heart sounds were normal. The abdomen was soft and nontender with no organomegaly or fluid. Results of a neurologic examination were noncontributory.

Diagnostic testing. White blood cell count was 12,800/µL, with 80% polymorphonuclear leukocytes and 20% lymphocytes; the hemoglobin level was 10.2 g/dL; and the platelet count was 156,000/µL. A peripheral smear showed normocytic normochromic anemia. The erythrocyte sedimentation rate was 124 mm/h.

Further studies disclosed the following: glucose, 92 mg/dL; blood urea nitrogen, 12 mg/dL; creatinine, 0.8 mg/dL; sodium, 138 mEq/L; potassium, 4 mEq/L; chloride, 100 mEq/L; total bilirubin, 1 mg/dL; conjugated bilirubin, 0.6 mg/dL; total protein, 7.8 g/dL; albumin, 3.2 g/dL; alkaline phosphatase, 118 U/L; aspartate aminotransferase, 24 U/L; alanine aminotransferase, 21 U/L.

The results of 2 blood cultures were negative for organisms. Serologic evaluation for Coccidioides yielded negative results. Serum ferritin was 350 ng/mL; serum iron was 38 µg/dL, and total iron-binding capacity was 200 µg/dL. Urinalysis results were normal.

A chest radiograph and sputum evaluation for acid-fast bacilli (AFB) were ordered.

The chest radiographs (Figures 1 and 2) showed alveolar infiltrate in the right upper lobe, with no hilar adenopathy. The cardiac configuration was normal. The sputum showed AFB (Figure 3). These findings in a person with RA who has been treated with infliximab and has a 3-week history of respiratory symptoms strongly suggested pulmonary TB.

Discussion. The pathogenesis of rheumatoid disease progression involves high concentrations of tumor necrosis factor (TNF), the central component in the cascade of cytokines induced in RA that stimulates production of additional inflammatory mediators such as chemokines, prostaglandins, proteases, and growth factors that activate neutrophils, β cells, and endothelial cells.

The TNF inhibitors infliximab, etanercept, and adalimumab are widely used to reduce the erosive damage of RA. TNF inhibitors are usually given to patients with active, progressive RA who have not responded satisfactorily to one or more conventional disease-modifying antirheumatic drugs such as methotrexate, sulfasalazine, hydroxychloroquine, and cyclosporine.

Although the TNF inhibitors are effective, neutralization of TNF significantly suppresses the immune response. This has led to an increased risk of such infections as tuberculosis (TB), Pneumocystis infection, and disseminated histoplasmosis.

Mycobacterial infections have been reported in a small percentage of patients who have undergone TNF therapy. Most infections appear to occur in the first 6 to 8 months of treatment. Extrapulmonary presentations, which have been reported in 30% to 50% of cases, include fever of unknown origin, miliary TB, TB-associated lymphadenopathy, peritonitis, enteritis, meningitis, and vertebral and bladder disease.

Pulmonary manifestations usually consist of chronic productive cough, hemoptysis, pleuritic chest pain, and dyspnea associated with constitutional symptoms such as fever, night sweats, lack of energy, and weight loss.

A high index of suspicion is warranted. The diagnosis is confirmed by demonstration of AFB either in biopsy material or sputum, in conjunction with sputum culture results. Chest radiography or computed tomography can be helpful.

Treatment. Once the diagnosis has been established, prompt and aggressive therapy is started with isoniazid, rifampin, ethambutol, and pyrazinamide. The regimen is continued for 2 months, followed by isoniazid and rifampin therapy for an additional 7 to 10 months.

According to guidelines from the American Thoracic Society and the Centers for Disease Control and Prevention, patients with active RA who are being considered for TNF inhibitor therapy may be at high risk for TB and should undergo tuberculin skin testing.¹ Induration of more than 5 mm is considered a positive result. 

Anti-TB prophylaxis therapy should be considered for any high-risk patient before TNF inhibitors are administered. Suggested courses of therapy are 1 month if the tuberculin skin test is positive, and 3 to 4 months if the patient has active TB.¹

Patients also should be evaluated for evidence of other preexisting infections. TNF inhibitors are best avoided in patients with chronic infections such as hepatitis B. Concomitant illnesses such as optic neuritis, multiple sclerosis, aplastic anemia, interstitial lung disease, and systemic lupus erythematosus may be exacerbated by TNF inhibitor therapy. Live vaccination is contraindicated in patients receiving TNF inhibitors.

Outcome of the case. Results of a tuberculin skin test were positive, with an induration of 22 mm. Test results for Mycoplasma, Chlamydia, and urinary Legionella antigen were negative. Sputum culture revealed Mycobacterium tuberculosis that was sensitive to all anti-TB drugs.

The patient initially was treated with ceftriaxone and azithromycin. After the diagnosis was made, the regimen was changed to isoniazid, rifampin, ethambutol, and pyrazinamide. Her fever resolved and her cough improved. The patient was discharged after a week, with instructions to take all 4 medications for 2 months and then to continue with isoniazid and rifampin for 10 more months.

The patient’s husband and 3 children also underwent tuberculin skin testing. Three had indurations of 10 mm; a 9-month course of isoniazid prophylaxis was prescribed.

Reference:

1. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med. 2000;161(4 pt 2):S221-S247.