A case of Lymphogranulamatosis beninga

Naresh Mullaguri MDResident PhysicianDepartment of NeurologyUniversity of Missouri

Chief complaintIntermittent shaking of bilateral lower extremities

19 year old RH AA male patient who was referred to Dr. Asher’s clinic by his PCP for the evaluation of his intermittent bilateral lower extremity shaking which has been going on for 7 years. He saw his PCP for new onset Headaches, loss of appetite and Weight loss. He also noticed some dark spots in his visual fields for one and half month. He had a shaking spell in the PCP office which led to the referral.

Headaches are bilateral in the temporo-parietal regions can radiate to the occipital region and neck. Can last anywhere between 6 hours to a whole day, throbbing in nature with pulsatile quality and associated with nausea and sensitivity to light. He denied trying any pain medications. He remember going to bed with headaches but was never awakened with them in the middle of the night. Never had any such type of headaches in the past. In the ER it was 4/10 in intensity. No correlation with change in posture, eye movements, bearing down, lying down or walking. Associated with spells of blurring of vision which can last anywhere between 1-10 minutes affecting both eyes with occasional complete loss of vision. In between the spells he mentioned that he can see okay.

HISTORY OF PRESENT ILLNESS

Tremors were intermittent, lasts anywhere between 10min to an hour and doesn’t interfere with walking, standing and associated with anxiety. For the past 7 years it is unchanged. Occurs 3-4 times a day, tremors in the hands, sometimes interferes with writing, varies in amplitude. Noticed worsening of the tremor when pressure was applied to the muscles of the arms like taking blood pressure.

He was found to have some papilledema and he was advised to get admitted to the Neurology service for further evaluation.

He was sent to Ophthalmology for the confirmation of the eye findings.

ROS is positive for night sweats, irregular fast heart rate, cough, occasional vomiting, constipation, bladder and bowel incontinence occasionally. Endorsed spell of ringing in ears, altered smelling and taste for 15-20 min and feeling of lack of drive and fatigue. Increased movements of legs during the sleep.

Reported loss of appetite, Loss of sex drive, Stopped smoking as he lost interest in it. Mentioned that he is experiencing hot flashes, light headedness and palpitations associated with blurring of the vision.

PERTINENT HISTORIES

PMH: Paranoid Schizophrenia in 2010 but not being following up with Psychiatry. Mentioned that he is not hearing any voices latelyRanitidine and Promethazine by his PCPNKDASingle, Finished 10th grade, works at a restaurant and denies drinking, Quit smoking 1 week ago but used to smoke ½ - 1 PPD, Denied recreational drug use, Denied any unprotected sexual intercourse or STI in the past.Migraines in mother, Maternal grand mother and great grandmother had Nervous break downs, Don’t know any history from the paternal side. Positive for DM, Cancer, HTN and CAD

MY FLOW OF THOUGHT

?Dealing with a systemic disease with focal neurological symptomsSounds like demyelinating diseases like MS or NMO – age of presentation and involvement of CN II and a ton of other constitutional symptomsI miss HIV, Tuberculosis but its counterpart Sarcoidosis, Lyme’s, opportunistic infections here in the US and he is an African American? May be an unfortunate guy with cancer/Autoimmune issues

Lets go to exam

Vital signs:Temperature: 37.2PR: 85, RegularRR: 16BP: 110-120/70-80s BMI: 24 (Weight loss from 210 – 188 pounds)

General: Well dressed, well spoken African American male, looks appropriate for the age. Not in distressHENT: Atraumatic, no rash or vesicles noticed, Oral mucosa is moist, external auditory canals were patent and normal. No tonsillar hypertrophy or pharyngeal wall erythema, No PNS tenderness. No thyromegaly, No wasting of facial muscles.Respiratory system: Non labored breathing, No wheezes, ClearCardiovascular System: S1 and S2 heard, No pedal edemaGastrointestinal: Soft, no tenderness or organomegaly palpatedMusculoskeletal: No joint effusion, tenderness or wasting.Integument: No rash, clubbing

Neurological: Higher Mental functions: Alert, oriented X 4, Speech is fluent and comprehension is intact. Able to follow multistep commands.

Cranial Nerves: Visual fields are full to confrontation, EOM were intact, Pupils were unequal with right one being 7mm and sluggishly reacting to light and the left one is 5mm and briskly reacting to light with relative afferent pupillary defect on the right side (May be confounded by the dilated fundus exam done by ophthalmology). Dilated fundus exam revealed edematous optic disc, retinal Vasculitis, Uveitis and crystalline deposits in the vitreous. Unable to confirm Papilledema. No facial asymmetry or sensory loss to pin prick, temperature and light touch, uvula is in midline and elevates symmetrically, Tongue protrudes to midline with good strength, Shoulder shrug is 5/5 bilaterally.

Motor exam: Tone is normal, Bulk is equal, Strength is 5/5 in all the extremities both proximally and distally, No tremors noticed, No dystonia observed. Gait is normal, able to do tandem walking, walk on his heels and toes. Good arm swing and sharp turns, No postural instability. No Bradykinesia.

Sensory exam: Intact to pin prick, vibration and temperature in all the four extremities with no sensory level. Romberg’s sign is negative.

Coordination: Intact to finger to nose and hell to shin test bilaterally, No dysdiadochokinesia.

Differential Diagnosis

Optic neuritis/Papillitis secondary to HIV, Sarcoidosis, Tuberculosis, Lyme’s disease, syphilis or other opportunistic infectionsMultiple Sclerosis/Neuromyelitis and other autoimmune diseases like Behcet’s disease, Lupus and Sjogren syndrome.CNS Vasculitis/Autoimmune Vasculitis (systemic like PAN)Lymphoma or other forms of cancer

INVESTIGATIONSNormal CBCNormal BMPALT – 57ESR – 21Flow cytometry – NegativeNormal Thyroid profileCSF : clear and colorless, Protein – 84, Glucose – 47, WBC – 46 (93% Lymphocytes), RBC – 7, Lactic Acid – 1.7UA is clean

MBP – 2.04

ACE level – High at 64 (Upper normal – 53)

Bartonella henselae titres elevated

MS profile Negative

HIV – Non reactive

Histoplasma, Blastomyces, Aspergillus, coccidioidomycosis, Toxoplasmosis, Toxocara, Lyme’s serology, Crypto, VDRL in CSF were negative, Vasculitis and autoimmune panel is negative.

Hepatitis panel is negative, Protein electrophoresis is negative

CSF culture, Blood cultures were negative.

IMAGING FINDINGSMRI of the Brain – Both Orbit and Optic nerves are

normalNo infarction, Midline structures were unremarkable. Venous anomaly in the pons but otherwise unremarkable pre and post contrast study.MRA of the Head and Neck is unremarkable to check vasculitis.Chest Xray is normal with no hilar prominenceChest CT showed Mediastinal and Bilateral hilar confluent Lymphadenopathy with differential including Granulomatous disease, Lymphoma and metastatic diseaseSubcarinal Lymph node fine needle aspirate : No malignant cells, Non-Necrotizing Granuloma

DIAGNOSIS SYSTEMIC SARCOIDOSIS

CANDLE WAX APPERANCE OF CHORIORETINAL VASCULITIS

CHORIORETINITS

Pulmonary involvement – almost always

Honey combing of Lung

HILAR LYMPHADENOPATHY

Non Caseating granuloma – Schaumann body

Neurosarcoidosis

Sarcoidosis is a multistep disease characterized by granulomatous inflammation.

5-15% of sarcoidosis patient have CNS involvement. Involves both CNS and PNS.

Symptoms including Headaches, Visual impairment, diplopia, ataxia, motor deficits, seizures, cognitive decline. Ocular involvement typically presents as Uveitis and rarely as orbital involvement affecting EOM and lacrimal glands.

Cranial NeuropathiesMeningeal disease: Aseptic Meningitis, Mass lesionHydrocephalusBrain disease: Endocrinopathy, Encephalopathy, micro vasculopathy, Seizures, stroke, vegetative dysfunction, extra or intramedullary spinal canal disease, Cauda equina syndromeNeuropathy: Mononeuropathy - axonal are demyelinating, sensory/ motor/sensorimotorMyopathy: Polymyositis, modules and atrophy

clinical presentation

CNS Sarcoidosis – Other symptoms to review with patient

Menses, Libido, GalactorrheaExcessive thirst – Osmostat, DI, Hyperglycemia, Hypercalcemia, HypercalciuriaAltered body temperature, sleep and appetite

LABSTFTs(Hypothalamic Hypothyroidism), Prolactin, Testosterone or Estradiol, FSH, LH and cortisol

Other Diagnosis to be considered Multiple sclerosis Neuromyelitis optica Sjogren syndrome Systemic lupus erythematosus Neurosyphilis NeuroborreliosisHIVLymphomaBehcet’s diseaseVogt – Koyanagi – HaradaToxoplasmosisBrucellosis

• Whipple’s disease• Germ cell tumors• Craniopharyngioma• Isolated CNS angitis• Primary CNS neoplasia• Lymphocytic Hypophysitis• Pachymeningitis• Rosai-Dorfman disease• CMV Meningoencephalitis• Low CSF pressure/volume

and Meningeal enhancement

IMAGING SPECTRUM

R. Shah et al. AJNR Am J Neuroradiology 2009;30:953-961

DURAL INVOLVEMENT

EXTRA-AXIAL MASSES

Leptomeningeal involvement

PARENCHYMAL LESIONS

CRANIAL NERVE AND EXOCRINE GLAND

INVOLVEMENT

SPINAL CORD AND NERVE ROOT INVOLVEMENT

SUPRA-SELLAR INVOLVEMENT

TREATMENT AND PROGNOSIS

Patient was discharged with oral taper of steroids with follow up appointment with Rheumatology.Spontaneous resolution in 4-6 monthsDamage may be permanent.Long term treatment is needed with Steroids and steroid sparing drugs

THANK YOU

Photo taken by Naresh Mullaguri in Illinois from an AMTRACK