# Clinical Cases: Neurodegenerative and Demyelinating Diseases ## Case 1: Alzheimer's Disease ### Patient Presentation **Demographics:** 74-year-old male **Chief Complaint:** Memory problems and getting lost while driving (brought by wife) **History of Present Illness:** The patient's wife reports that over the past 2-3 years, her husband has had gradually worsening memory problems. Initially, he began misplacing items and forgetting recent conversations. Over the past year, this has progressed significantly. He forgot their granddaughter's birthday party that happened last week but remembers details from their wedding 50 years ago. He got lost driving to their church, which they have attended for 30 years. He has asked the same questions repeatedly and has difficulty managing their finances, which she has now taken over. He has become more withdrawn and less interested in his hobbies. The patient minimizes his symptoms, saying "my memory is fine for my age." **Family History:** Mother had "dementia" in her 80s **Physical Examination:** - Vital signs: Normal - General: Pleasant, well-groomed male who defers questions to wife - Neurological: - Mental status: Alert; oriented to person and city but not date (says "sometime in spring" when it's October); poor recall of recent events - Montreal Cognitive Assessment (MoCA): 18/30 (impaired in delayed recall 0/5, orientation 4/6, abstraction, and clock drawing) - Language: Mild word-finding difficulty; circumlocution; comprehension intact - Cranial nerves: Intact - Motor: 5/5 throughout; no parkinsonism - Sensory: Intact - Reflexes: 2+ symmetric; frontal release signs (palmomental reflex present) - Gait: Normal **Workup:** - **MRI brain:** Bilateral hippocampal atrophy (more prominent than expected for age); moderate generalized cortical atrophy; no vascular changes; Fazekas grade 1 white matter changes - **Laboratory:** TSH normal; B12 normal; RPR negative; CBC, CMP normal - **Amyloid PET:** Positive (diffuse cortical amyloid deposition) - **CSF (optional, obtained for confirmation):** Decreased A-beta 42, increased phospho-tau, increased total tau - consistent with Alzheimer's pathology **Diagnosis:** Alzheimer's disease dementia, moderate stage (NIA-AA criteria) **Treatment:** - Donepezil 5 mg daily, increased to 10 mg after 4-6 weeks (cholinesterase inhibitor) - Memantine to be added when disease progresses to moderate-severe stage - Discussed newer anti-amyloid therapies (lecanemab); patient not a candidate due to moderate stage (most effective in early disease) - Driving evaluation recommended; advised to stop driving given getting lost - Safety assessment: removed firearms from home; stove knob covers installed - Caregiver support resources provided to wife - Advanced care planning discussion **Clinical Course:** At 6-month follow-up, the patient's wife reported some stabilization in his memory with donepezil, though mild GI side effects initially. He accepted not driving after the formal driving evaluation recommended against it. His wife joined a caregiver support group. The family completed healthcare proxy and advance directive documentation while the patient could still participate in discussions. **Clinical Pearl:** Alzheimer's disease is characterized by insidious onset and gradual progression, with memory impairment (especially for recent events) as the earliest and most prominent feature. Patients often have limited insight (anosognosia). The pattern of better remote memory with impaired recent memory reflects hippocampal involvement in encoding new memories while consolidated long-term memories are stored elsewhere. Biomarkers (amyloid PET, CSF A-beta/tau) now allow definitive diagnosis during life. Disease-modifying therapies (anti-amyloid antibodies) are most effective when started early. --- ## Case 2: Multiple Sclerosis - Relapsing-Remitting ### Patient Presentation **Demographics:** 28-year-old female **Chief Complaint:** Right eye vision loss and leg weakness **History of Present Illness:** The patient developed pain with eye movement in her right eye 5 days ago, followed by progressive vision loss over 3 days. She describes the vision as "looking through wax paper." Her color vision is particularly affected - reds look "washed out." She now recalls that 2 years ago, she had an episode of numbness and tingling in her legs lasting 3 weeks, which she attributed to stress and never sought medical attention for. **Physical Examination:** - Vital signs: Normal - General: Healthy-appearing young woman - Neurological: - Mental status: Normal - Cranial nerves: - Visual acuity: Right eye 20/200 (left eye 20/20) - Color vision: Cannot identify Ishihara plates with right eye - Pupils: Right relative afferent pupillary defect (RAPD) - when light swings to right eye, both pupils dilate (Marcus Gunn pupil) - Fundoscopy: Right optic disc slightly swollen (papillitis) - Other cranial nerves normal - Motor: 5/5 throughout - Sensory: Decreased vibration sense at toes bilaterally - Reflexes: 3+ throughout; bilateral Babinski signs - Coordination: Normal - Gait: Normal **Key Findings:** - Optic neuritis (right) - Prior episode of transverse myelitis (history of leg numbness) - Signs of prior spinal cord involvement (hyperreflexia, Babinski) - = Dissemination in space AND time **Workup:** - **MRI brain with and without contrast:** Multiple ovoid T2/FLAIR hyperintense lesions in periventricular white matter oriented perpendicular to the ventricles ("Dawson's fingers"); several juxtacortical lesions; one enhancing lesion (active); one infratentorial lesion - **MRI spine:** Two non-enhancing T2 lesions in cervical cord - **MRI orbits:** Right optic nerve enhancement and swelling - **Lumbar puncture:** Oligoclonal bands present in CSF (absent in serum); elevated IgG index; mild lymphocytic pleocytosis (12 cells) **Diagnosis:** Multiple sclerosis, relapsing-remitting (McDonald 2017 criteria satisfied) **Treatment:** *Acute Optic Neuritis:* - IV methylprednisolone 1 gram daily for 3 days - Oral prednisone taper over 2 weeks *Disease-Modifying Therapy:* - Discussed options: moderate efficacy (interferons, glatiramer) vs high efficacy (ocrelizumab, natalizumab) - Started ocrelizumab (anti-CD20) given multiple lesions indicating active disease - Baseline JCV antibody: Negative - Hepatitis B screening: Negative *Other:* - Vitamin D supplementation (2000 IU daily) - Smoking cessation counseling (she is a social smoker) - Discussed pregnancy planning (ocrelizumab has washout period) **Clinical Course:** Visual acuity improved to 20/30 at 6 weeks; color vision partially recovered. No new relapses occurred on ocrelizumab over 1 year. Surveillance MRI showed no new or enhancing lesions. She remained fully functional, working full-time as an accountant. **Clinical Pearl:** Multiple sclerosis diagnosis requires dissemination in space (lesions in multiple CNS locations) and time (new activity over time or simultaneous enhancing and non-enhancing lesions). Optic neuritis is often the presenting manifestation - the triad of painful eye movement, vision loss, and RAPD is classic. Oligoclonal bands in CSF are present in >95% of MS patients. Early treatment with highly effective disease-modifying therapy prevents accumulation of disability. Dawson's fingers (periventricular lesions perpendicular to ventricles) are characteristic of MS and reflect perivenular inflammation. --- ## Case 3: Amyotrophic Lateral Sclerosis (ALS) ### Patient Presentation **Demographics:** 62-year-old male **Chief Complaint:** Progressive weakness in right hand for 6 months **History of Present Illness:** The patient first noticed weakness in his right hand 6 months ago, manifesting as difficulty turning keys and buttoning shirts. Over the past 3 months, the weakness has spread to involve his right arm more diffusely, and he has noticed his left hand becoming weak as well. He has also noticed "twitching" in his arm muscles and has lost weight (15 lbs) due to decreased appetite. His wife notes his speech has become slightly slurred in the past month. He denies numbness, tingling, or pain. He denies bladder or bowel problems. **Physical Examination:** - Vital signs: Normal; weight 72 kg (down from 87 kg) - General: Thin male; visible muscle wasting in hands; fasciculations visible in upper arms - Neurological: - Mental status: Alert, oriented; cognition grossly intact; mildly dysarthric speech - Cranial nerves: - Tongue: Fasciculations visible; mild atrophy; deviates slightly right on protrusion - Jaw jerk: BRISK (UMN sign) - Facial sensation and strength: Normal - Gag: Present - Motor: - Inspection: Atrophy of bilateral thenar and interosseous muscles; fasciculations in deltoids, biceps, and paraspinals - Tone: Increased in lower extremities (spasticity) - Strength: - Right grip 3/5, finger abduction 3/5, wrist extension 4/5, shoulder abduction 4/5 - Left grip 4/5, finger abduction 4/5, wrist extension 4+/5, shoulder 5/5 - Bilateral hip flexion 4+/5, knee extension 5/5, ankle dorsiflexion 4+/5 - Sensory: INTACT throughout (no sensory involvement) - Reflexes: 3+ throughout upper and lower extremities; bilateral Babinski signs present; jaw jerk brisk - Gait: Slightly spastic **Key Findings:** - Combined upper motor neuron signs (spasticity, hyperreflexia, Babinski) AND lower motor neuron signs (atrophy, fasciculations) in the SAME regions - Multiple body regions affected (bulbar, cervical, thoracic, lumbosacral) - Sensory system SPARED - Bladder/bowel function SPARED **Workup:** - **EMG/Nerve conduction studies:** Widespread denervation (fibrillations, positive sharp waves, large motor unit potentials) in multiple regions (tongue, cervical and lumbar myotomes, thoracic paraspinals); sensory nerve conductions NORMAL - **MRI brain and cervical spine:** No structural lesions; no cervical cord compression - **Laboratory:** CK mildly elevated (420 U/L); otherwise normal including normal glucose, thyroid, B12 - **Pulmonary function tests:** FVC 68% predicted (early respiratory muscle involvement) **Diagnosis:** Amyotrophic lateral sclerosis (El Escorial criteria: Definite ALS - UMN and LMN signs in 3 regions) **Treatment:** - Riluzole 50 mg twice daily (modest survival benefit) - Edaravone IV infusion cycles (slows functional decline) - Multidisciplinary ALS clinic enrollment (neurology, pulmonology, nutrition, PT/OT, speech therapy, social work) - Nutritional support (PEG tube discussed for future) - Non-invasive ventilation (BiPAP) initiation given reduced FVC - Advance care planning **Clinical Course:** The patient's weakness progressed over the following months. He began using BiPAP at night when FVC dropped to 50%. A PEG tube was placed at 9 months when swallowing became unsafe. He participated actively in advance care planning, electing not to pursue tracheostomy and mechanical ventilation. He died peacefully at home 22 months after diagnosis, surrounded by family. **Clinical Pearl:** ALS is characterized by the combination of upper motor neuron signs (spasticity, hyperreflexia, Babinski) and lower motor neuron signs (atrophy, fasciculations, weakness) WITHOUT sensory involvement. The presence of both UMN and LMN findings in the same myotome is the diagnostic hallmark - no other condition reliably produces this combination. Eye movements and bladder/bowel function are typically spared until late. Median survival is 3-5 years, with respiratory failure being the most common cause of death. Riluzole provides modest survival benefit; supportive care (nutrition, ventilation) significantly improves quality of life. --- ## Clinical Image ![Multiple sclerosis periventricular lesions MRI](case_01_image.jpg) **Image Description:** Axial FLAIR MRI of the brain demonstrating characteristic periventricular white matter lesions in multiple sclerosis. The ovoid lesions are oriented perpendicular to the lateral ventricles, forming the classic "Dawson's fingers" pattern that reflects perivenular demyelination along the medullary veins. **Attribution:** Image from Radiopaedia (https://radiopaedia.org/), Creative Commons Attribution-NonCommercial-ShareAlike 3.0 license.