CNS Pathology Lab Case Studies

1. CNS Pathology LabCase Studies Dr. Gilbert WebPath

2. Case 2 • History: • This 61 year old alcoholic male was sitting on a bar stool when he was noted to suddenly fall to the floor. He was unable to arise and the paramedics were called. When they arrived, he was able to answer questions and he stated that he had a severe headache. Upon arrival to the hospital the admitting physical examination demonstrated a right hemiparesis. The patient became increasingly somnolent after admission. • Further history: • In spite of supportive care, the patient became comatose and died two hours after admission.

3. Slide 1.1This is a CT scan of the patient's head upon admission.

4. Slide 1.2This is a coronal section of the brain and midbrain at autopsy.

5. Questions: • What are possible causes of this acute incident? • What treatment could have prevented this event? • Is there any treatment after the event occurs?

6. Answers: • What are possible causes of this acute incident? There are several possibilities. Because of the acuteness of the symptoms, one should think of a vascular problem, either due to trauma or to underlying vessel disease. This man could have suffered a skull fracture and epidural hemorrhage upon hitting the floor. Embolic stroke, hypertensive bleed (from long-standing hypertension), or bleed from a vascular malformation are all possible. Bleeding into a tumor is another possibility. • What treatment could have prevented this event? Treatment of hypertension with antihypertensive medication over the years has produced a marked reduction in the incidence of hypertensive bleeds in the brain. • Is there any treatment after the event occurs? Evacuation of the blood from a hypertensive bleed in this location is rarely helpful. Hypertensive bleeds into the cerebellum can be life saving, if evacuation is performed before tonsillar herniation and brainstem compression.

7. Case 2 • History: • This 81 year old man was in good health until developing a cough with the production of yellow sputum. He complained to his relatives of a headache the day before admission. He was found stuporous by his son on the day of admission. In the emergency room, the physical examination demonstrated an elderly man who was not responding very well to questions. His temperature was 99.7 degrees F, respirations 16, pulse 100 and weak, and blood pressure 110/50. His neck was stiff. A lumbar puncture revealed cloudy cerebrospinal fluid with a marked pleocytosis with 1500 WBC's (90% of them PMN's), decreased glucose, and mildly elevated protein. • Further history: • The patient does not respond to treatment and dies.

8. Slide 2.1This is a gross photograph of his brain.

9. Slide 2.2This is a microscopic photograph with H&E staining of the subarachnoid space.

10. Questions: • What is the diagnosis? What is the most likely organism in this man? • What would be your treatment? • What is a possible cause of death in this man?

11. Answers: • What is the diagnosis? What is the most likely organism in this man? Acute meningitis is the diagnosis. The most likely organisms are bacteria; meningitis in this age group is most commonly caused by Streptococcus pneumoniae. • What would be your treatment? Immediate institution of intravenous penicillin. • What is a possible cause of death in this man? Uncal and tonsillar herniation with brainstem compression can occur because of brain edema.

12. Case 3 • History: • This 68 year old man was noted by his family to have become forgetful in the months before being seen by his family physician. He was brought to his physician by his son because he had been found wandering in the streets. On physical examination, he was unable to remember any objects after five minutes and, although an avid football fan, he was unable to recount the previous Monday night's game which he had watched with his son. A CT scan was obtained and showed mild cerebral atrophy.

13. Slide 3.1This is the gross appearance of the brain from a man who died from the same disease suffered by this patient.

14. Slide 3.2This is a microscopic section of brain stained with H&E.

15. Slide 3.3This is another microscopic section of brain stained with a silver stain. In the center there is a senile plaque.

16. Questions: • What is the apparent diagnosis? • What other tests would you order on this man? • What are the major causes of dementia?

17. Answers: • What is the apparent diagnosis? Dementia is the most likely diagnosis, although depression in the elderly must be ruled out. • What other tests would you order on this man? Thyroid funtion tests, vitamin B12 level, and serologic test for syphilis (e.g., VDRL) will help rule out more treatable causes of dementia. A toxicology screen will help rule out possible unknown drugs. • What are the major causes of dementia? Alzheimer's disease, multi-infarct dementia, hydrocephalus, chronic subdural, and diffuse Lewy body disease are major causes for dementia. Pick's disease is uncommon. Dementia can be seen late in Parkinson's disease. Alzheimer's disease is by far the most common.

18. Case 4 • History: • This 58 year old alcoholic male developed increasing weakness on his right side over several days. Upon admission he was mildly agitated and complaining of a headache. His right arm and leg were weak and there was flattening of the nasolabial fold on the right. He denied any recent head trauma. A head CT scan was obtained.

19. Slide 4.1This is the CT scan.

20. Slide 4.2This is a gross photograph of a similar lesion in a patient who died.

21. Questions: • What are the possible causes for his weakness? • Why did the patient deny any history of recent trauma? • What age groups commonly present with this type of lesion after head trauma? • What blood vessels are rupture to produce this lesion?

22. Answers: • What are the possible causes for his weakness? A progressive stroke due to vascular occlusion on the left side or an enlarging subdural are possible causes in spite of the negative history of trauma. An intraparenchymal tumor or abscess are other possibilities. • Why did the patient deny any history of recent trauma? With his history of alcoholism, he most likely was intoxicated (drunk) at the time and did not remember striking his head. • What age groups commonly present with this type of lesion after head trauma? Subdural hematomas are most commonly seen in the very young and the very old. Alcoholics commonly present with subdurals because of their propensity to fall. • What blood vessels are rupture to produce this lesion? The crossing dural veins are ruptured. Because of the slower accumulation of blood, the patient may not present acutely with the symptoms of a space occupying mass. Chronic subdurals are thought to be caused mainly by minor movements of the head, tearing the small vessels taking part in the resorption of the original clot.

23. Case 5 • History: • This 52 year old man had presented at age 37 with blurred vision. This lasted for several weeks. Five years later he suffered an episode ofright leg weakness which resolved over several months. Over the ensuing 10 years he developed dysarthria, internuclear ophthalmoplegia, and paraplegia with spasticity. He became bedridden and died of a pulmonary embolus. At the time of his initial evaluation, a spinal tap revealed a normal CSF pressure, 6 cells (all lymphocytes), an elevated protein, and a normal glucose. Protein electrophoresis revealed an elevation in IgG. An MRI was performed six years before his death and showed several T2 bright images in the white matter of the cerebral hemispheres.

24. Slide 5.1This is a CT scan from another patient with the same disease.

25. Slide 5.2This is a gross photograph of the brain from this patient.

26. Slide 5.3This is a microscopic section with myelin stain of one of the lesions.

27. Slide 5.4This is a microscopic section with a silver stain for axons of one of the lesions.

28. Slide 5.5On this H&E stained microscopic section, note the perivascular lymphocytes in the lesion.

29. Answers: • What is the most likely diagnosis? Multiple sclerosis. • What other test would help in confirming your diagnosis? What would you tell the patient about the prognosis? CSF agarose gel electrophoresis to look for oligoclonal bands. Visual evoked responses and brain stem evoked responses may demonstrate abnormalities not noted on examination. The prognosis varies with each patient and many patients do not progress to severe disabilities. Many patients have periods of remission.

30. Case 6 • History: • This 50 year old female was in her normal state of good health when she began to notice a funny feeling in her left hand. Over the ensuing weeks she began to notice a continual nagging headache which was partially relieved with Tylenol. On the morning of admission she had a grand mal seizure witnessed by her husband. Upon arrival at the emergency room she was awake and slightly disoriented but could give a good history. On physical examination there was mild weakness of the left arm and leg with paresthesias of the left hand.

31. Slide 6.1This is an enhanced MRI scan of the right hemisphere as seen sagittally.

32. Slide 6.2This is an H&E stained microscopic section of the biopsy taken from the lesion.

33. Slide 6.3This is a gross photograph of a similar lesion from an elderly man who died.

34. Questions: • What are possible causes for these symptoms? • What would be part of your workup on this patient?

35. Answers: • What are possible causes for these symptoms? Since the symptoms progressed over weeks, tumor or abscess should be considered. A chronic subdural is another possibility. • What would be part of your workup on this patient? A scan to rule out a localized lesion. CT scans are better at identifying intracranial hemorrhages, while MRI scans are better at identifying neoplasms.

36. Case 7 • History: • This 25 year old female was admitted to the hospital for left sided focal seizures and obtundation. She had complained of increasing headaches over the weeks prior to admission. There was also some clumsiness of her left hand and leg. She noted clonic jerking of her right arm lasting approximately five minutes which resolved with some weakness in her arm. Twenty minutes later, a similar episode occurred. On admission she was barely responsive and had a temperature of 100 degrees F. She had a right hemiparesis.

37. Slide 7.1This is an enhanced head CT scan. Describe the lesion present.

38. Slide 7.2This is a gross photograph of a section of brain from another patient with the same problem.

39. Slide 7.3This is a microscopic section with connective tissue (trichrome) stain of the lesion after some months have passed.

40. Questions: • What are the possible causes for this type of presentation? • What studies would help define this situation? • What further studies would help define the etiology of the lesion in the brain? • How would you treat her disease? What is the prognosis?

41. Answers: • What are the possible causes for this type of presentation? Because of the fever one would think of infection. With the focality of the symptoms and the progression of symptoms over several weeks, an abscess would be suspected. Tumor would also have to be considered. • What studies would help define this situation? Scans would help localize a lesion and define what type of lesion was present. • What further studies would help define the etiology of the lesion in the brain? Blood cultures might isolate an organism. An echocardiogram might localize the source of infection. A chest x-ray might also help localize a source of infection. • How would you treat her disease? What is the prognosis? Antibiotics specific to the organism would be given. If subsequent scans did not show improvement, surgical drainage could be considered. The prognosis with response to therapy is good.

42. Case 8 • History: • This 55 year old man presented with the acute onset of left sided headache and mild right leg paresis. On CT scan a focal area of hemorrhage was seen near the gray white junction in the mid left frontal area. There was a questionable lesion in the right parietal lobe, but this was not well defined. It was decided to evacuate the lesion because of the mild mass effect and symptoms. • Further history: • On questioning, the patient admitted to noting some blood-tinged urine in the weeks prior to his admission. He did not have any dysuria or urgency. A CT scan of the abdomen revealed a large mass in the right kidney.

43. Slide 8.1This T1 weighted post-contrast MRI scan in coronal view demonstrates the lesion. The mass lesion is brightly enhancing and could represent either blood or a neoplasm.

44. Slide 8.2This microscopic section shows the cellular portion of the lesion evacuated and sent to surgical pathology.

45. Slide 8.3This gross section of the brain is from another individual with the same disease. There is a well circumscribed hemorrhagic lesion in the cortex with some surrounding edema.

46. Questions: 1. What are the possible etiologies for this lesion? What would be your follow-up after the discovery of the lesion? 2. What is the most likely diagnosis which explains both lesions? What is the treatment?

47. Answers: • What are the possible etiologies for this lesion? What would be your follow-up after the discovery of the lesion? Primary or metastatic tumor are possible etiologies. Follow-up consists of a more thorough exam and history to see if there is a primary tumor elsewhere in the body. Special stains can be done on the biopsy tissue to discern whether it is primary or metastatic. In general, well circumscribed tumors in brain are metastatic. The pattern of clear cells would suggest renal cell carcinoma. 2. What is the most likely diagnosis which explains both lesions? What is the treatment? A renal cell carcinoma is the most likely diagnosis. Surgical removal of the kidney and a search for possible other metastatic sites is indicated.