Maria Ana Autria Dalangin Medicine II PAPER CASE III Clinical Neurology Case of RT, 48 y/o male patient from Tondo, Manila, works as a pedicab driver, admitted in a tertiary hospital because of seizures. 3 weeks PTA low to moderate grade remittent fever and episodes of headache. He was still able to work even with the bifrontal headaches. 2 weeks PTA fever persisted; worsening headaches occurring almost throughout the day and associated with episode of vomiting. This time, patient spent most the time bedridden and was no longer able to work. No consult was done. A week PTA relatives noted that the patient moves only the right side of the body (left-sided paralysis); there is profound drowsiness. There is bedwetting and persistence of remittent fever. At this time, patient sleeps almost all the time. A day PTA with the persistence of fever and other manifestations, patient 2 episodes of generalized seizures described as stiffening of extremities, cyanosis and cyanosis and drooling of saliva, hence present admission. Pertinent historical data: Wife died a year ago due to an unknown lung disease (?) Chronic alcoholic drinker and heavy cigarette smoker Shabu user for 3 years PE: Stretcher-borne, unconscious, hyposthenic, in cardiorespiratory distress BP= 130/90 mmHg; CAR= 110/min; RR= 28/min; T= 38.5 C With lymphadenopathies in the neck Symmetrical chest expansion; rales and wheezes present on all lung field areas Scaphoid abdomen; normoactive bowel sounds; with hepatomegaly
Neurologic exam: Stuporous with mild grimacing and withdrawal only to painful stimuli Pupil are anisocoric right pupil is unreactive to light 5 mm; left pupil is sluggishly reactive 2-3 mm (+) papilledema – bilateral There is deviation of the eyeballs to the right side (+) central left facial paralysis seen during grimacing Impaired gag response 0/5 left arm and leg +++ DTR left extremities; ++ DTR right extremities (+) Babinski sign, left Neck is rigid to passive flexion Questions to be answered: 1. Explain the clinical findings by doing clinicoanatomical correlation. 2. Formulate at least 3 differential diagnosis and defend their bases. 3. Give your final diagnosis and propose a pathophysiological mechanism. 4. State your diagnostic and therapeutic plans. I. II. SALIENT FEATURES 48 y/o male CC: seizures
remittent fever and episodes of headache 2 weeks PTA fever persisted; worsening, headaches, episode of vomiting. A week PTA right side of the body (left-sided paralysis), profound drowsiness, bedwetting A day PTA with the persistence of fever and other manifestations patient 2 episodes of generalized seizures cyanosis and cyanosis and drooling of saliva Family and social history o Wife died a year ago due to an unknown lung disease (?) o Chronic alcoholic drinker and heavy cigarette smoker o Shabu user for 3 years PE: o o o Stretcher-borne, unconscious, hyposthenic, in cardiorespiratory distress With lymphadenopathies in the neck Symmetrical chest expansion; rales and wheezes present on all lung field areas
Neurologic exam: Stuporous with mild grimacing and withdrawal only to painful stimuli Pupil are anisocoric right pupil is unreactive to light 5 mm; left pupil is sluggishly reactive 2-3 mm (+) papilledema – bilateral There is deviation of the eyeballs to the right side (+) central left facial paralysis seen during grimacing Impaired gag response 0/5 left arm and leg +++ DTR left extremities; ++ DTR right extremities (+) Babinski sign, left Neck is rigid to passive flexion III. 1. NEUROLOGICALLocalization Is there a neurological disorder? Yes, patient presented seizure, signs of increased ICP and left sided hemiparalysis 2. Where is the lesion? The inflammation is in the right hemisphere of frontal lobe with concomitant abnormalities at the brainstem and with compression of spinal cord and increase intracranial pressure. Patients Vomiting Clinicoanatomic localization General elevation of intracaranial pressure → increase pressure on the floor of fourth ventricle → vomiting Frontal lobe abscess Reticular formation of the brainstem though thalamocortical projection → activates cerebral cortex → maintain consciousness (Intact RF in the brainstem) Right hemisphere impression Increase ICP
patient moves only the right side of the body (left-sided paralysis) Stuporous with mild grimacing and withdrawal only to painful stimuli Pupil are anisocoric right pupil is unreactive to light 5 mm; left pupil
Contralateral hemiparesis Disconnection anywhere in this pathway due to the compression or the effect on the brainstem of the meningitis
Fixed, dilated pupil on the ipsilateral side due to compression of cranial nerve III
is sluggishly reactive 23 mm (+) papilledema – bilateral Rise in CSF pressure will compress the thin walls of the retinal veins as it crosses the extension of the subarachnoid space to enter the optic nerve → bulging forward of the optic disc → edema of the disc → papilledema Increase ICP
There is deviation of the eyeballs to the right side (+) central left facial paralysis seen during grimacing Impaired gag response UMN in the Left sensorimotor cortex or in the course of corticobulbar fibers Touch the lateral wall of pharynx with spatula- pharyngeal muscle contract → afferent runs into CN9 → efferent neuron runs into CN9 (stylopharyngeus) and CN10 (pharyngeal constrictor muscles) cortical and spinal area Spinal reflexes
Palsies of cranial nerves III, V, or VI, lateral rectus muscle weakness This lesions cause weakness only of the muscles innervating the lower part of the face on the contralateral side. The muscle of the brows is usually spared due to the small amount of direct bilateral input of the cerebral cortex to the LMN of both the facial nerve that controls the forehead muscles. Possible lesion - glossopharyngeal and vagus nerve
0/5 left arm and leg +++ DTR left extremities; ++ DTR right extremities (+) Babinski sign, left
Right cortical function and spinal function is intact. Left function may be inactivated by compression of the cerebral hemisphere Normal right reflex and dysfunction to the left side of the body owing to the compression or inflammation of the right hemisphere of the brain Babinski is normally present during the 1st year of life because the corticospinal tract is not myelinated until the end of the first year but in the case of the patient, the possible lesion in the corticospinal tract render this pathway nonfunctional, thus the influence of the other descending tracts on the toes become apparent and a kind of withdrawal reflex takes place in response to stimulation of the soles. Pathognomonic sign of meningeal irritation
Upper motor neuron lesion specifically lesions of the corticospinal tract
Neck is rigid to passive flexion 3.
Nuchal rigidity
What is the nature of the lesion? The lesions are mainly foci of metastatic caseous lesions due to infection of Mycobacterium tuberculosis bacilli.
4. IV.
What are the diagnostic plans to confirm the nature of the lesion? We could request for the lumbar tap then send specimen for culture and AFB smear DIFFERENTIAL DIAGNOSIS 1. Subdural Empyema
Subdural empyma was ruled in due to the presence of Headache, Hemiparesis or hemiplegia, Seizure and vomiting. Also the patient mental status changes stupor which is very common in subdural emopyema. The presence of Meningismus or meningeal signs, Hemiparesis or hemisensory deficits, Papilledema and other features of increased ICP, such as nausea/vomiting and
mental status changes to stuporous are also exhibited by the patient however it was ruled out due to the lack of recent history (<2 wk) of sinusitis, otitis media, mastoiditis, meningitis, cranial surgery or trauma, sinus surgery, or pulmonary infection Speech difficulty (dysphasia) which was very indicative of SDE 2. Meningococcal Meningitis
Meningococcal meningitis is ruled in because it is characterized by acute onset of intense headache, fever, nausea, vomiting and stiff neck. Neurological signs include nuchal rigidity and an altered mental state which is also present in the patient. However it was ruled out due to the greater incidence of the disease in younger patient and also patient usually present with rash and in severe cases patients have rapid circulatory collapse and a hemorrhagic rash. 3. Brain Abscess
Brain abscess is considered due to the presentation of headache, fever, seizure, hemiparesis, and the presentation of increase intracaranial preassure such as papilledema, vomiting and altered mental status which is the same with our patient however the evolution of signs and symptoms are more variable with brain abscess than the tuberculous subacute meningitis. Due to the lack of laboratory workup like LP and MRI we could not totally rule out the abcess. 4. Viral Meningitis
Upon presentation, most patients report fever, headache, irritability, nausea, vomiting and stiff neck like in our patient. The classic tetrad of meningitis is fever, meningismus, irritability, and photophobia. The examination reveals no focal neurological deficits in the majority of cases. However he doesn’t have rashes and headache is characterized as ―worst headache of my life‖ in viral meningitis. And the incidence of viral meningitis is also very common in children. V. PRIMARY IMPRESSION SUBACUTE MENINGITIS SPECIFICALLY TUBERCULOUS MENINGITIS Undiagnosed Pulmonary Tuberculosis Left hemiparesis T/C Brain Abscess We are presented with a case of a 48 year old male, TB infection rates are consistently higher for men, and living in Tondo which is probable a congested place that is very susceptible for communicable diseases. He was admitted due to seizure attack which as we go through the history may be owed to his chronic alcohol intact and might have a possibility of withdrawal syndrome if he stops or the used of methamphetamine which caused drug induced seizure. Upon PE, rales and wheezes is present in all lung fields which may be indicative of undiagnosed pulmonary TB. Having a history that his wife died of unknown lung disease is gives him an increase risk for TB. Patients presents with unrelenting headache, stiff neck, low-grade fever, and stupor which is typically a subacute meningitis. Cranial nerve abnormalities like the palsies of cranial nerves III, V, or Vi and lateral rectus muscle weakness which was presented by deviation of the eyeball, impaired ga response where we could think of possible lesion on the CN 10 and 9 and the anisocoric pupil that suggest CN III compression. Left sided hemiplegia and positive babinski sign of the left gives an impression of both UMN and LMN lesions. Laterality owing to the right side of the brain which manifest contralaterally to the left. The presence of a positive nuchal rigidity indicates a meningeal irritation. VI. PATHOPHYSIOLOGY Tuberculous meningitis is usually caused by the acid-fast organism Mycobacterium tuberculosis and exceptionally by Mycobacterium bovis or Mycobacterium fortuitum. Rich described two stages in the pathogenesis of the meningitis: 1. 2. first a bacterial seeding of the meninges and subpial regions of the brain with the formation of tubercles, followed by the rupture of one or more of the tubercles and the discharge of bacteria into the subarachnoid space.
The meningitis may occur as a terminal event in cases of miliary tuberculosis or as part of generalized tuberculosis with a single focus (tuberculoma) in the brain.
Mycobacterium tuberculosis bacilli enter the host by droplet inhalation
infection of the alveolar macrophage
Localized infection escalates within the lung
meningitis.
dissemination to the regional lymph nodes to produce the primary complex
significant bacteremia
Tubercles rupturing into the subarachnoid space bacilli seed to the meninges or brain parenchyma
tubercle bacilli to other organs in the body
Brain
VII.
DIAGNOSTIC PLAN
We should request for the ff laboratory: Lumbar tap Complete blood count Erythrocyte sedimentation rate Electrolytes: Mild-to-moderate hyponatremia is present in roughly 45% of patients, in some cases constituting a true syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Serum glucose level BUN and creatinine levels Serology for syphilis Complementation test or its equivalent for fungal infections Urinalysis Cerebrospinal fluid should also be requested: For Cell counts, differential count, cytology, Glucose level, with a simultaneous blood sugar level, Protein, Acid-fast stain, Gram stain, appropriate bacteriologic culture and sensitivity, India ink, Cryptococcal antigen, herpes antigen, Culture for M tuberculosis (50-80% of known cases of TBM yield positive results), Polymerase chain reaction (PCR): Results imply that PCR can provide a rapid and reliable diagnosis of TBM, although false-negative results potentially occur in samples containing very few organisms (<2 colony forming units (CFU)/mL), and Syphilis serology for possible syphilitic etiology
These laboratories will help us determine the classic CSF abnormalities in tuberculous meningitis: (1) (2) (3) (4) elevated opening pressure, lymphocytic pleocytosis (10 to 500 cells/uL) elevated protein concentration in the range of 1 to 5 g/L (10 to 500 mg/dL) decreased glucose concentration in the range of 1.1 to 2.2 mmol/L (20 to 40 mg/dL).
Imaging Studies such as X-ray and CT scan/ MRI can be requested. Although CT scan and MRI lack specificity, they help in monitoring complications that require neurosurgery. Chest radiography: Posteroanterior and lateral views may reveal the following: Hilar lymphadenopathy Simple pneumonia Infiltrate Fibronodular infiltrate/cavitation Pleural effusion/pleural scar CT scan and MRI of the brain reveal hydrocephalus, basilar meningeal thickening, infarcts, edema, and tuberculomas The characteristic CT finding is a nodular enhancing lesion with a central hypodense lesion (Weisberg, 1984). Contrast enhancement is essential. Early stages are characterized by low-density or isodense lesions, often with edema out of proportion to the mass effect and little encapsulation. At a later stage, well-encapsulated tuberculomas appear as isodense or hyperdense lesions with peripheral ring enhancement.MRI and CT scan are critical for the diagnosis of TBRM, revealing loculation and obliteration of the subarachnoid space along with linear intradural enhancement. THERAPEUTIC INTERVENTION
VIII.
The treatment of tuberculous meningitis consists of the administration of a combination of drugs—isoniazid (INH), rifampin (RMP), and a third and sometimes a fourth drug, which may be ethambutal (EMB), ethionamide (ETA), or preferably pyrazinamide (PZA). All of these drugs have the capacity to penetrate the blood-brain barrier, with INH, ETA, and PZA ranked higher than the others in this respect. Resistant strains are emerging, which require the use of PZA and ETA in addition to the two main drugs (INH and RMP). Antibiotics must be given for a prolonged period, 18 to 24 months as a general rule (although it may not be necessary to give all three or four drugs for the entire period). Isoniazid is the single most effective drug. Surgical Care In patients with evidence of obstructive hydrocephalus and neurological deterioration who are undergoing treatment for TBM, placement of a ventricular drain or ventriculoperitoneal or ventriculoatrial shunt should not be delayed. Studies suggest that prompt ventriculoatrial or ventriculoperitoneal shunting improves outcome, particularly in patients presenting with minimal neurological deficit.Unless a mass effect is compromising vital structures, and surgical intervention rarely is required in the treatment of tuberculomas. (From journal TBM February 7, 2006- emedicine) Supportive therapy should be also given especially fro the seizure of the patient References: Kasper, K.L. et al (2005) HARRISON'S PRINCIPLES OF INTERNAL MEDICINE. 16th Edition. USA,McGraw-hill companies, Inc. Ong, W.T. et al (2003) Medicine Blue Book. 5th edition.Mandaluyong,Philippines. Ganong, W.F. Review of Medical Physiology. 18th edition. USA, Appleton and Lange Gilman, S. et al (1997) Manter and Gatz’s Essential of Clinical Neuroanatomy and Neurophysiology 9 th edition.Thailand, book Promotion and service Ltd. Snell, R.S. Ph.D Clinical Neuroanatomy for Medical Students Victor - Adams & Victor's Principles Of Neurology 7th ed eMedicine