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Tuberculosis (TB), in its various forms, is a challenging problem in many areas of the world. Tuberculous meningitis (TBM; shown), also known as meningeal tuberculosis, is the most common presentation of neurotuberculosis and accounts for approximately 1% of all TB cases. The case-fatality rate for untreated TBM is almost 100%, and a delay in treatment may lead to permanent neurologic damage. Therefore, prompt diagnosis is essential to allow timely initiation of antitubercular therapy. Modern neuroimaging is the cornerstone in the early diagnosis of central nervous system (CNS) tuberculosis and may prevent unnecessary morbidity and mortality due to treatment delay.
Image courtesy of Medscape.
An 18-year-old Pakistani man presents with a 4-week history of low-grade fever, headache, and vomiting. On examination, he has left cranial nerve (CN) III, IV, and VI palsies and right CN VI palsy. Signs of meningeal irritation are present. Magnetic resonance imaging (MRI) of the brain with contrast is performed, with the results shown in the slide.
Which of the following radiologic findings is/are apparent on MRI?
Images courtesy of Sumaira Nabi, MBBS, FCPS.
Answer: C. Hydrocephalus with basal meningeal enhancement.
In the images shown, the red arrows indicate dense enhancement of the basal meninges, whereas the blue arrows highlight the bulbous and dilated temporal horns of the lateral ventricles, which are indicative of hydrocephalus. The thick exudate of TBM leads to CN dysfunction, as seen in this patient. Hydrocephalus results from obstruction of the basilar cisterns by this exudate.[1]
Images courtesy of Sumaira Nabi, MBBS, FCPS.
Cranial nerves that are more commonly involved in TBM include CN III, CN IV, CN VI, CN VII, CN IX, and CN X.[1] The photographs in the slide are from the same patient, demonstrating the CN dysfunction in the form of left complete ophthalmoplegia and right CN VI palsy on ocular motility testing.
Images courtesy of Sumaira Nabi, MBBS, FCPS.
A young man with history of AIDS presents with fever and altered sensorium. MRI of the brain with contrast reveals multiple ring enhancing lesions. The radiologist reports these as tuberculomas against the background of TBM.
Which of the following tests is the gold standard for confirming this clinical suspicion?
Images courtesy of Sumaira Nabi, MBBS, FCPS.
Answer: B. Acid-fast bacillus (AFB) culture and sensitivity testing of CSF.
CSF culture is the gold standard for the diagnosis of TBM; however, it is tedious and time-consuming, and its sensitivity is low (~40-80%). It should be performed to determine drug susceptibility, as well as to establish the diagnosis. Either Löwenstein-Jensen (LJ) medium (shown) or BACTEC (BD, Franklin Lakes, NJ) can be used for culturing Mycobacterium tuberculosis.[3]
Image courtesy of Wikimedia Commons.
In one study, tuberculomas were reported in 53% of patients with TBM.[2] Tuberculomas result from parenchymal Rich foci and are among the most common manifestation of CNS TB. They are frequently multiple. In the same study, tuberculomas were multiple in 82.4% cases and solitary in 17.6%.[2] Tuberculomas are usually located on both sides of the tentorium. Solitary lesions can be either supratentorial or infratentorial, mostly arising in the basal ganglia/thalami and the cerebellar hemispheres. Tuberculomas can present as a hypointense core with rim enhancement or as nodular lesions with diffuse enhancement; the former pattern is more common.[2,3] In the images in the slide, which represent coronal views from MRI of the brain with contrast, the blue arrows mark infratentorial tuberculomas, whereas the red arrow marks a supratentorial tuberculoma.
Images courtesy of Sumaira Nabi, MBBS, FCPS.
A 30-year-old Pakistani man presents with a 7-day history of right-side weakness and altered mentation. This was preceded by a 6-week history of low-grade fever. On examination, the patient has a Glasgow Coma Scale (GCS) score of 9/15 with right hemiplegia. Marked neck stiffness is evident, and the Kernig sign is positive. Noncontrast computed tomography (CT) of the brain depicts an infarct in the territory of the left middle cerebral artery. Routine examination of CSF reveals a white blood cell (WBC) count of 312 with 98% mononuclear cells. The protein level is 481 mg/dL, and the glucose level is 19 mg/dL. India ink stain of CSF is negative, and AFB smear is positive, leading to a diagnosis of TBM with infarction.
Which of the following is the most likely cause of infarction in TBM?
Image courtesy of Sumaira Nabi, MBBS, FCPS.
Answer: C. Obliterative endarteritis.
The blue arrows denote a hypodense area in the territory of the left middle cerebral artery, which suggests an infarction. The red arrow marks the concomitant hydrocephalus. TBM is a documented cause of cerebrovascular disease and stroke. The proposed mechanism is considered to be vasculopathy. When the exudate in TBM infiltrates the cortical or meningeal blood vessels, it leads to inflammation and obliterative endarteritis, eventually causing infarction and stroke.[1,2]
Image courtesy of Sumaira Nabi, MBBS, FCPS.
A 35-year-old Pakistani man presents with a 6-week history of generalized headache and continuous fever and a 1-week history of unconsciousness preceded by altered behavior. He has a history of marked weight loss during this period; however, he has no history of cough, chest pain, or night sweats. On admission, the patient looks chronically ill and is cachectic, pale, and febrile (38.5°C). On neurologic examination, he has a GCS score of 4/15 (E1V2M1) and exhibits neck stiffness. Motor examination shows spastic quadriparesis. CT of the brain is performed (shown; see also slide 11).
Images courtesy of Shahzad Ahmed, MBBS.
CT of the brain (shown; see also slide 10) illustrates significant dilatation of the ventricular chain with sulcal effacement, findings consistent with hydrocephalus.
Which of the following is the best option for definitive management of hydrocephalus in this patient?
Images courtesy of Shahzad Ahmed, MBBS.
Answer: D. Ventriculoperitoneal (VP) shunt.
Medical management might be offered as first-line therapy to patients with communicating hydrocephalus or those with Medical Research Council (MRC) grade I or II TBM. Medical options include steroids, dehydrating agents (eg, mannitol), diuretics (eg, furosemide), and acetazolamide to reduce CSF production. Surgical management of hydrocephalus in patients with TBM includes tapping of the ventricles through burr holes, lateral and third ventriculostomy, and VP shunt placement. Since the early 1980s, VP shunting has remained the shunt procedure of choice for patients with TBM and hydrocephalus. In the image shown in the slide, the blue arrow marks the hydrocephalus, whereas the red arrow marks the entry of the shunt tubing into the lateral ventricle.[4,5]
Image courtesy of Medscape.
VP shunts divert CSF from the lateral ventricles of the brain into the peritoneal cavity by way of subcutaneous tubing. One end of the tubing is placed into the dilated lateral ventricles, and the other end empties into the peritoneal cavity. The system includes a valve to control the rate of drainage. VP shunting is the most common and best treatment option for most cases of hydrocephalus.
Image courtesy of Medscape adapted by Sam Shlomo Spaeth.
A 15-year-old boy presents with a 2-month history of headache and fever and a 1-week history of ptosis of the left eyelid. On examination, he has neck stiffness in conjunction with partial nonfatigable ptosis of the left eye with normal extraocular motility and pupillary reflex. Contrast MRI of the brain reveals a solitary tuberculoma (shown).
Which of the following is the location of the lesion causing the ptosis?
Image courtesy of Sumaira Nabi, MBBS, FCPS.
Answer: B. Thalamus.
Thalamic lesions produce a variety of ocular motility deficits, including vertical gaze palsy, pupillary and lid abnormalities (eg, ptosis), third-nerve palsy, and nystagmus. Most commonly, the underlying pathology is vascular, as is seen in stroke; however, various kinds of space-occupying lesions and infective lesions (eg, tuberculomas) have also been reported in the literature, and this case is one such example. Ptosis is defined as a drooping upper eyelid. A wide range of acquired causes exists, including thalamic lesions.
Image courtesy of Medscape.
A 33-year-old man presents with a 6-day history of worsening headache associated with transient visual obscurations. He also has a 2-month history of low-grade fever and vomiting. On examination, he has bilateral papilledema (shown) and left CN VI palsy. Signs of meningeal irritation are present. Lumbar puncture shows an elevated opening pressure of 40 cm H2O. Analysis of CSF and MRI of the brain yield results suggestive of TBM. A magnetic resonance (MR) venogram is normal. Perimetry demonstrates an enlarged blind spot on both sides.
Which complication of TBM has this patient developed?
Image courtesy of Wikimedia Commons.
Answer: C. Idiopathic intracranial hypertension (IIH).
IIH, also referred to as pseudotumor cerebri (PTC) or benign intracranial hypertension (BIH), is a condition characterized by elevated CSF pressure in the brain and signaled by headache, vomiting and visual disturbance. Fundoscopic examination reveals papilledema (arrows), which may range in severity from mild (left) to severe with hemorrhage and exudates (right). The disorder must be recognized as soon as possible because it can lead to progressive loss of vision and eventually to permanent blindness. There are a number of different causes of IIH, and CNS tuberculosis is one of them. The exact cause of IIH is seldom identified. In countries where TB is endemic, TBM must be ruled out when a patient presents with IIH.
Images courtesy of Wikimedia Commons.
A 40-year-old female with HIV infection and TBM who has been on antitubercular therapy for 3 months presents to the neurology clinic with subacute weakness of all four extremities and reports difficulty in walking and bladder dysfunction for 3 weeks. On neurologic examination, the patient’s muscle strength is 1/5 in both lower limbs and 3/5 in the upper limbs. Deep tendon reflexes are brisk. Plantar responses are extensor. Impaired sensations are present to the level of C5. MRI of the cervicodorsal spine with and without gadolinium contrast shows altered signals from C1 to T4. Findings are suggestive of acute transverse myelitis secondary to tuberculosis. Aquaporine-4 antibody and antinuclear antibody (ANA) testing yield negative results.
Which of the following is the most appropriate next step in treatment?
Image courtesy of Shahzad Ahmed, MBBS.
Answer: A. High-dose steroid therapy.
The images in the slide are from MRI of the cervicodorsal spine with and without gadolinium contrast, which shows altered MR signals from C1 to T4. This area appears hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, with no significant postcontrast enhancement (see also slide 20), findings suggestive of acute transverse myelitis in association with TBM. Such patients are best treated with high-dose corticosteroids.
Image courtesy of Shahzad Ahmed, MBBS.
The image in the slide shows no postcontrast enhancement (see also slide 19). Half of the cases of CNS TB involve the spine. Intramedullary involvement, in the form of radiculomyelitis, transverse myelitis, or intraspinal tuberculomas, is quite rare; extramedullary disease, in the form of caries of the spine or arachnoiditis, is more common and better known. Transverse myelitis typically extends for no more than two spinal segments, whereas longitudinal extensive transverse myelitis (LETM) extends for three or more spinal segments. Although LETM is usually a characteristic feature of neuromyelitis optica (NMO), the literature does describe patients with spinal tuberculosis who present with LETM and a clinical profile that does not fulfill the diagnostic criteria for NMO, as is the case in this particular instance.
Image courtesy of Shahzad Ahmed, MBBS.
A 65-year-old Pakistani man presents with a 3-month history of low-grade fever and backache, which was followed by progressive weakness of both legs and loss of bladder control for 1 month. On examination, the patient has spastic paraparesis with brisk deep tendon reflexes and extensor plantar responses. He has severe tenderness with deformity in the lower thoracic spine. The erythrocyte sedimentation rate (ESR) is 120 mm/hr at the end of the first hour. MRI of the dorsolumbar spine shows a gibbus deformity in the lower dorsal spine with extensive destruction of T11 and T12 along with the intervening disc. There is a fusiform collection of low intensity on T1-weighted imaging and high intensity on T2-weighted imaging, which is indicative of abscess secondary to Pott disease.
Which of the following is the most appropriate treatment measure in this case?
Images courtesy of Shahzad Ahmed, MBBS.
Answer: C. Surgery followed by antitubercular therapy.
Spinal TB (Pott disease), first described in 1782 by Sir Percival Pott, is a common disease in the developing world. Backache is the usual presenting symptom, commonly accompanied by limb weakness, sensory involvement, and sphincteric dysfunction, depending on the degree of compression. The tubercle bacillus erodes the cancellous bone and eventually destroys the cortex. The infection gradually spreads from the disc space to the adjacent vertebra. In advanced stages, progressive vertebral collapse ensues and leads to kyphosis and gibbus formation. The best diagnostic modality for spinal TB is MRI of the spine with and without gadolinium contrast; it is more sensitive and specific than radiography and CT. The arrows in the slide mark the extensive destruction of T11 and T12 along with the intervening disc. Fine-needle aspiration (FNA) biopsy of the vertebrae done under CT guidance for cytologic, histologic, and bacteriologic studies is recommended for further confirmation of the diagnosis.[6]
The mainstay of treatment is antitubercular chemotherapy for 12 months, which is effective in 90% of cases. Surgical decompression is not routinely indicated except, as in this scenario, in cases of significant compression with risk of permanent neurologic sequelae or in cases of abscess formation.
Image courtesy of Shahzad Ahmed, MBBS.
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