NEUROLOGY I: Clinico-Pathological Conference Group 4

Class 2016A

Acha, Alfonso, Andan, Arevalo, Baring, Blancaflor, Cabili, Canlas, Catbagan, Colet, Dayos, Dela Paz, Dizon JP., Espelimbergo, Fernandez KD., Gabor, Gepes, Guingon, Jamito, Lacambra

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CASE Health History The patient is a 61-year old female with the chief complaint of decreased hearing on the right ear for 19 years duration with no accompanying tinnitus, headache, disequilibrium, gait imbalance, pain or discharge. 8 months prior to consultation, she complained of right facial numbness with an approximation of 70% and darkening of vision with dizziness and blurring. 2 months prior to consultation, the patient had intermittent headache and progression of hearing loss on the right ear. It wasn’t accompanied by fever, upper respiratory infection, syncope, tinnitus, or any history of trauma. The patient is a known hypertensive for 10 years. Her medications are Amlodipine10mg OD for 10 years and Irbesartan/Hydrochlorothiazide150/12.5mg OD in 2013. She has reported a family history of hypertension and none of diabetes mellitus and cancer. She is not a smoker and alcohol drinker

Review of systems revealed the following information: occasional 2-pillow orthopnea, occasional easy fatigability with 1 flight of stairs. There were also no palpitations, chest pains, cough and colds, fever, vomiting, abdominal pain, dyspnea and chest tightness. Physical Exam General

Awake, alert, oriented, not in cardiorespiratory distress BP: 120/80 mmHg; HR 84 bpm; RR: 18 cpm; Temp: 36.2 oC Anicteric sclera, pink palpebral conjunctivae, no tonsillopharyngeal congestion, no

CLADS No pallor, warm, good skin turgor, no lesions Equal chest expansion, clear breath sounds, no crackles, no retractions Adynamic precordium, normal rate regular rhythm, distinct S1 & S2, no murmurs Soft, flabby, normoactive bowel sounds, no tenderness, no masses Full and equal pulses, no cyanosis, no edema

Neurological Awake, coherent, conversant, with good attention span; fluent speech No R-L disorientation, no finger agnosia, no acalculia Intact immediate, recent, and remote memory; oriented to time, place, and person Can recognize familiar objects, color

Cranial Nerves I - Can identify test substance on both nostrils II - 3-4 mm Equal, brisk reaction to light on the Right; with Left homonymous superior quadrantanopsia III, IV, VI - primary gaze midline, intact Extraocular movements V - v1, v2, v3 - right 80%, left 100% facial sensation; normal masseter and temporalis tone VII - no facial asymmetry VIII - intact gross hearing on left ear only, lateralization on the left, positive Rinne test both ears IX, X - uvula in midline, able to swallow, (+) gag reflex right, weak gag on left XI - good shoulder shrug, good SCM and trapezius tone XII - tongue in midline, no atrophy, no fasciculation

Motor Normal tone/bulk 5/5 motor strength

Sensory 100% intact to pin-prick light touch temp vibration sense all extremities

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Reflexes ++ on both biceps, triceps, brachioradialis, knee, ankle reflexes (-) Babinski, (-) Hoffmans sign Cerebellum no nystagmus, dysmmetria, dysdiadochokinesia Meninges (-) Kernigs, (-) Brudzinski Gait Ataxic PERTINENT DATA Health History Pertinent Positives

1. The patient is a 61-year old female with the chief complaint of decreased hearing on the right ear for 19 years duration with no accompanying tinnitus, headache, disequilibrium, gait imbalance, pain or discharge

2. 8 months prior to consultation, she complained of right facial numbness with an approximation of 70% and darkening of vision with dizziness and blurring

3. 2 months prior to consultation, the patient had intermittent headache and progression of hearing loss on the right ear.

4. Known hypertensive for 10 years Pertinent Negatives

1. She has reported a family history of hypertension and none of diabetes mellitus and cancer.

2. Occasional 2-pillow orthopnea 3. Occasional easy fatigability with 1 flight of stairs.

Physical Exam Cranial Nerves

II - Left homonymous superior quadrantanopsia V - v1, v2, v3 - right 80%, left 100% facial sensation VIII - intact gross hearing on left ear only, lateralization on the left, positive Rinne test both ears IX, X - weak gag on left Ataxic Gait

DISCUSSION Interpretation of the Pertinent Data from the Neurological Exam

With the given results of the neurological exam of the patient, the following tables contain the implications the components of the neurologic exam and how they contribute to the disease presented by the patient. Table 1. The cortical findings based on the neurologic PE and their interpretation.

Findings Interpretation

Awake, alert, oriented, coherent, conversant, good attention span

The executive functioning of the patient is intact indicating that there is no frontal lobe involvement.

Conversant, fluent speech Intact speech would indicate non-involvement of the Broca’s area of the frontal lobe and of the Wernicke’s area of the parietal lobe.

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No R-L disorientation, no finger agnosia, no acalculia

These findings indicate that there is no involvement of the parietal lobe, specifically that of the dominant hemisphere.

Intact immediate, recent and remote memory

These findings indicate that there is no involvement of the dominant temporal lobe which is the center for memory. Preservation of recent memory would also indicate an intact pre-frontal area in the frontal lobe.

Can recognize familiar objects and colors

Color perception is centered in the occipital lobe. Furthermore, interpretation of sensations such as when recognizing familiar objects is under the control of the parietal lobe. These would indicate no involvement of these areas.

Table 2. The negative cranial nerve findings and their interpretation.

Findings Interpretation

CN I – Can identify test substance on both nostrils

This indicates that both the peripheral and central parts of the olfactory pathway are unaffected. The proximity of this pathway to the cortical areas support the idea that the lesion is not located in the upper, cortical parts of the brain.

CN III, IV, VI – primary gaze midline, intact EOMs

These findings indicate that the oculomotor pathways are unaffected. Thus the lesion would not be located in the areas where these pathways travel through. These would include the central part of the midbrain ventral to the periaqueductal gray where the oculomotor (III) and trochlear (IV) nuclei are located and the area of the pons just ventral to the 4th ventricle where the abducens nuclei are located. Furthermore, the respective areas each nerve would traverse in the brainstem would not be involved. These would include the interpeduncular fossa of the anterior brainstem (for III), the posterior aspect of the midbrain at the level of the inferior colliculi (IV) and the anterior part of the pontomedullary junction near the midline (VI).

CN VII – No facial asymmetry

The area of the facial nucleus is preserved, which is in the pontine tegmentum.

CN XI – Good shoulder shrug

The SVE nuclei are preserved which are in the dorsal part of the anterior horn of the upper cervical spinal cord. Also, the nerve is intact which means the lateral aspect of the lower medulla would be unaffected.

CN XII – Tongue in midline, no atrophy, no fasciculation

The area of the hypoglossal nucleus is intact which is found ventral to the 4th ventricle along the length of the medulla at the midline. The anterior part of the medulla, specifically around the area of the pyramids and the olives, is unaffected for the nerve emerges here.

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Table 3. Motor and sensory findings and their interpretation.

Findings Interpretation

Motor: Normal tone/bulk 5/5 motor strength

The corticospinal tract is intact. This means that along the brainstem the more anterior parts would be unaffected where the descending pathways course through.

Sensory: 100% intact to pinprick, light touch, temperature, vibration

The ascending pathways are intact, both the lateral spinothalamic and the spinal lemniscal system. Related to the brainstem, this would exclude a lesion that would occur in the more internal parts where the ascending pathways run.

Reflexes: ++ on both biceps, triceps, brachioradialis, knee, ankle - Babinski, - Hoffmans

The spinal cord is intact. There are no upper motor neuron lesions further supporting the absence of a lesion along the descending pathways in the brainstem.

Cerebellum: No nystagmus, no dysmetria, no dysdiadochokinesia

There is no involvement of the lateral or hemispheric zone of the cerebellum.

Meninges: - Kernigs, - Brudzinski

The meninges are not affected.

Table 4. PE and History findings, and their interpretation.

Findings Interpretation

Progressive unilateral hearing loss with lateralization to the left and positive Rinne test on both ears

Suggests right sensorineural hearing loss. It may therefore involve the cochlea (sensory), the cochlear nerve and nuclei (neural), or the central auditory pathways. Also, it is not accompanied by tinnitus and ear pain/discharge hence it is not caused by a primary ear disease. Dysfunction of neighboring cranial nerves points to either peripheral nerve lesion or cerebellopontine angle syndrome.

Left homonymous superior quandrantanopsia

Since it is binocular, the lesion can be localized to or beyond the optic chiasm. This type of visual field defect results from lesion in Lateral fibers of LGB or right Meyer loop OR lower part of geniculocalcarine tract (to the lingual gyrus)

Localization The lesion is located at the Right side of the brainstem affecting the right cerebellopontine angle and adjacent structures and extending upward to the right lateral geniculate body.

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Figure 1. Brainstem views

Based on the findings of the neurologic physical exam, it is most likely that the lesion

does not involve the higher levels of the nervous system. Table 5 summarizes these findings and highlights why the lobes of the cortical brain are unaffected. Intact reflexes as stated in Table 3 also indicate that the lesion does not involve the spinal cord. Since the higher levels and the spinal cord are said to be unaffected, the next likely area to consider is the brainstem and the findings of the neurologic examination of the cranial nerves would help to identify which parts of this structure are unaffected. First, intact smell further distances the lesion from the higher levels. The other findings combined, which have been summarized and interpreted in Table 2, would exclude the midbrain, the pontine tegmentum and the areas of the brainstem just ventral to the 4th ventricle. Furthermore, findings from Table 3 would suggest that there would be no involvement of the more anterior parts of the brainstem

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where the descending, motor pathways run and of the more internal parts of the brainstem where the ascending, sensory pathways run. The brainstem as the location of the lesion

Based on the findings summarized in Table 5, the lesion is most likely located external to the brainstem at its right side specifically in the cerebellopontine angle and extending upward to the right lateral geniculate body. This location allows all the structures related to the pertinent findings to be involved while affecting the least number of structures that do not show affectation in the patient. Structures internal to the brainstem are also visualized in Figure 3. The cerebellopontine angle (CPA) is a triangular space formed between the rostral medulla, the caudal border of the middle cerebellar peduncle and the adjacent part of the cerebellum (Figure 2). In this area, the facial (VII) and the vestibulocochlear (VIII) nerve would emerge.

Figure 2. The cerebellopontine angle (CPA) showing the external aspect of the lesion.

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Figure 3. Structures (boxed) within the brainstem affected by the lesion.

The right CPA would be an ideal site to localize the damage to the auditory pathway.

This is because the finding of hearing loss localized purely to the one ear with no affectation of the other side suggests that the affected structure within the auditory pathway is peripheral and external to the brainstem. The auditory pathways within the brain stem have heavy bilateral involvement, being composed of crossed and uncrossed fibers with the majority being crossed. Therefore, involvement of the inner structures of the brain stem appears unlikely since it must produce bilateral impairment of hearing. The inferior cerebellar peduncle which forms a boundary of the CPA is a likely structure involved in the manifestation of ataxic gait. Loss of function of the spinocerebellar fibers within the peduncle results in ataxia in the same side of the lesion. Furthermore, if the lesion is large enough it can extend to the cerebellum and impinge on the vermal zone which can also cause ataxia.

In addition, involvement of the vestibular nuclei could also contribute to ataxia. These contribute to the innervations that support the antigravity muscles of the body. The nuclei are located in the lateral part of the floor of the 4th ventricle in the level of the rostral medulla. They are just medial to the inferior cerebellar peduncle, thus could possibly be involved based on proximity.

A weak gag reflex on the left side could involve the right spinal nucleus of V at around the area of the pons and medulla, somewhat proximate to the area of the supposed lesion (Figure 9). The right nucleus mainly supplies fibers to the left nucleus ambiguus via the trigeminothalamic tract which then supplies the efferent arm of the reflex. This would give rise to the greater nerve fibers affected on the left side, thus giving rise to a weakened left gag reflex.

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Figure 4. Weak gag reflex arising from a lesion in the left caudal spinal nucleus of V, thus interrupting the major supply of fibers to the left nucleus ambiguus via the trigeminothalamic tract.

Facial numbness can be caused by a lesion extending to the sensory division of the trigeminal nuclear complex found in the posterolateral part of the tegmentum of the pons. Specifically, the right complex would be affected.

Finally, the presence of left superior homonymous quadrantanopia may indicate that the lesion has extended upward, affecting the right lateral geniculate body. Neurons of the LGB give rise to fibers that form the geniculocalcarine tract (optic radiations), which then projects to the primary visual cortex of the occipital lobe. A proportion of these fibers/axons form the Meyer’s loop. A problem in the right lateral geniculate body, therefore, may affect the optic radiation (Meyer’s loop) and damage the fibers of Meyer's loop and/or damage the temporal lobe portion of the optic radiation resulting in loss of input from the inferior half (superior visual field) of both contralateral hemiretinas (superior quadrantanopia). Other symptoms

Orthopnea could be the result of left congestive heart failure as a result of her hypertension of 10 years. When a person goes into the supine position (as in lying down), there is redistribution of blood from the lower extremities to a more equal distribution throughout the body. As a result there is an increased volume of blood returning to the heart. Patients with left ventricular heart failure are unable to pump out the excess blood causing a backup of blood. This backup will eventually hinder venous blood flow increasing pulmonary and capillary pressure causing interstitial pulmonary edema, increased airway resistance, decreased compliance and dyspnea. Being in an upright position, as in having more pillows under the patient, decreases the pressure and relieves symptoms. In the case of easy fatigability, this is one of the noted side effects of taking thiazide drugs such as hydrochlorothiazide or the drug irbesartan.

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Table 5. Pertinent Findings and areas affected by the lesion

SIGN/SYMPTOM AREA AFFECTED

Left homonymous superior quadrantonopia

Right Lateral Geniculate Body

Darkening of vision with blurring and dizziness

Right Lateral Geniculate Body

V - v1, v2, v3 - right 80%, left 100% facial sensation

Right Trigeminal nerve

Hearing loss for 19 years Right vestibulocochlear nerve

Weak gag reflex on the left Above the nucleus ambiguous (Contralateral side)

Ataxic Gait Right vestibulocochlear nerve

OTHER SIGN/SYMPTOM

Intermittent headache Growing mass on the cranial vault

Occasional 2-pillow orthopnea Complication of Hypertension

Occasional easy fatigability after climbing 1 flight of stairs

Complication of Hypertension

DIFFERENTIAL DIAGNOSES Acoustic Neuroma, also known as Vestibular Schwannoma is a benign tumor of vestibulocochlear nerve. It originates from Schwann cells of CN VIII in the internal auditory canal at the glial-Schwann cell junction. It is the most common tumor of cerebellopontine angle. It is characterized as a slow growing tumor (Thus, diagnosis is delayed.) and presents as hearing loss, tinnitus, ataxia, and vestibulopathy. Other symptoms include headaches and facial paresthesia. As the tumor grows, internal auditory meatus progressively widens, and complete ipsilateral nerve deafness ensues (tinnitus subsiding as deafness progresses). Progressive tumoral enlargement may account for hydrocephalus or signs and symptoms of increased ICP. Affected areas are variable to the direction of the expansion of the tumor. Medial tumor growth affects neighboring cranial nerves and eventually brainstem and ipsilateral cerebellar compromise occur with very large tumors. Anterior expansion of tumor affects trigeminal n. – facial numbness, paroxysmal facial pain, depressed ipsilateral corneal reflex – and abducens n. – weakness of ocular abduction, horizontal diplopia. Posteroinferior expansion of tumor affects CN IX and X – dysphagia, absent pharyngeal reflexes, vocal cord paralysis – and CN XI – ipsilateral SCM and trapezius paresis; facial n. is usually involved resulting in facial paresis, loss of taste on the ipsilateral anterior 2/3 of the tongue, decrease in ipsilateral tearing, and rarely, hyperesthesia of the posterior wall of the external auditory canal (Hitselberg sign).. It occurs more common in women and people aged 40-60 years old. MRI imaging is the most sensitive diagnostic procedure to detect it and also special views of auditory canal. Treatment is surgical if removal/debulking needed or stereotactic surgery.

The cerebellopontine angle may also be affected by meningiomas, which account for about 20% of the tumors that may arise in that area. Meningiomas may irritate the cortex, compress the brain and cranial nerves, and inflict injury upon the vascular supply of some areas. If it happens to be located at the cerebellopontine angle, it may also cause decreased hearing with a possibility of facial weakness and numbness. Though symptoms may be similar to what the patient is experiencing, meningiomas commonly lead to hyperostosis or an excessive growth of bone which causes chronic pain, a symptom which the patient has not reported. This condition is also rare, and an increased probability of having the condition is usually associated with an inherited disease called neurofibromatosis type 2.

A facial nerve neuroma, though rare, may also be considered as a differential diagnosis. The most common presenting complaint of a facial nerve neuroma is facial

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twitching followed by a progressive or sudden facial weakness. It may also obstruct the external auditory canal, causing hearing loss which is classified to be conductive. Despite the similarities this cannot be considered for the patient, because the results of the Rinne Test showed that air conduction was perceived to be louder than bone conduction—a positive result indicating sensorineural hearing loss.

Epidermoids may also be a possible diagnosis, and they originate from epithelial rest cells. They are found to be close to the brainstem, infiltrating some areas and causing it to have an irregular shape. Growth progresses slowly, however presenting symptoms with facial twitching as the most common finding usually appear during the ages of 20-30. It is unlikely that the patient has this condition, since the chief complaint of hearing loss began 19 years ago when the patient was 42 years old and he has no symptom of facial twitching evident.

A facial schwannoma, histologically similar to a vestibular schwannoma or acoustic neuroma, may also be considered. It mostly involves the geniculate ganglion, a part of the facial nerve that contains fibers and sensory neurons. Due to its involvement, the most common presenting symptoms are usually facial weakness, focal twitch, and/or full hemifacial spasm. If the patient were to have facial instead of acoustic schwannoma, it would be logical to think that the chief complaint would not be of hearing loss but of ipsilateral facial pain or weakness.

The following conditions may also be differential diagnoses, but they are extremely rare with only a few cases: glioma, hemangioblastoma, medulloblastoma, embryonic tumours, glomus tumours, hemangiomas,cholesterol granulomas and arachnoid cysts.

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